PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 29596829-5 2018 Recent studies suggest that pharmacological concentrations of the APL therapeutic drugs, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), affect post-mitotic nuclear import of the APL-associated oncoprotein PML/RARA. Arsenic Trioxide 124-140 PML nuclear body scaffold Homo sapiens 217-220 31214877-2 2019 It is reported that arsenicals can effectively degrade PML/RARalpha, such as arsenic trioxide and realgar. Arsenic Trioxide 77-93 PML nuclear body scaffold Homo sapiens 55-58 30662778-4 2018 We describe the efficacy and feasibility of the consecutive use of all-trans retinoic acid and arsenic trioxide-containing regimen for the treatment of promyelocytic leukemia and high-dose methotrexate plus cytarabine to treat lymphoproliferative involvement of the central nervous system. Arsenic Trioxide 95-111 PML nuclear body scaffold Homo sapiens 152-174 30259936-0 2018 Arsenic trioxide preferentially binds to the ring finger protein PML: understanding target selection of the drug. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 65-68 30259936-1 2018 Arsenic trioxide (ATO) is used in the clinic for the treatment of acute promyelocytic leukemia by targeting the protein PML. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 112-123 30259936-1 2018 Arsenic trioxide (ATO) is used in the clinic for the treatment of acute promyelocytic leukemia by targeting the protein PML. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 112-123 30026570-3 2018 Moreover, PML/RARA is specifically targeted by All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two agents that synergistically act to induce degradation of the oncoprotein. Arsenic Trioxide 82-98 PML nuclear body scaffold Homo sapiens 10-13 30026570-3 2018 Moreover, PML/RARA is specifically targeted by All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two agents that synergistically act to induce degradation of the oncoprotein. Arsenic Trioxide 100-103 PML nuclear body scaffold Homo sapiens 10-13 30693698-0 2018 [Involvement of PML proteins in treatment of acute promyelocytic leukemia with arsenic trioxide]. Arsenic Trioxide 79-95 PML nuclear body scaffold Homo sapiens 16-19 30693698-1 2018 Promyelocytic leukemia (PML) protein, a tumor suppressor, plays an important role in patients with acute promyelocytic leukemia (APL) receiving arsenic trioxide (As2O3) therapy. Arsenic Trioxide 144-160 PML nuclear body scaffold Homo sapiens 24-27 30693698-1 2018 Promyelocytic leukemia (PML) protein, a tumor suppressor, plays an important role in patients with acute promyelocytic leukemia (APL) receiving arsenic trioxide (As2O3) therapy. Arsenic Trioxide 162-167 PML nuclear body scaffold Homo sapiens 24-27 30824184-1 2019 Genetic mutations on PML-RARalpha in acute promyelocytic leukemia (APL) are reported to associate with arsenic trioxide (ATO) or all-trans retinoic acid (ATRA) resistance. Arsenic Trioxide 103-119 PML nuclear body scaffold Homo sapiens 21-24 30824184-1 2019 Genetic mutations on PML-RARalpha in acute promyelocytic leukemia (APL) are reported to associate with arsenic trioxide (ATO) or all-trans retinoic acid (ATRA) resistance. Arsenic Trioxide 121-124 PML nuclear body scaffold Homo sapiens 21-24 30824184-2 2019 Here we performed a retrospective analysis of APL patients and identified that the patient with S214L mutation on the PML moiety of PML-RARalpha showed resistance to both ATO and ATRA. Arsenic Trioxide 171-174 PML nuclear body scaffold Homo sapiens 118-121 30824184-2 2019 Here we performed a retrospective analysis of APL patients and identified that the patient with S214L mutation on the PML moiety of PML-RARalpha showed resistance to both ATO and ATRA. Arsenic Trioxide 171-174 PML nuclear body scaffold Homo sapiens 132-135 30763586-4 2019 ATO acts through a direct arsenic binding to cysteine residues in zinc fingers located in promyelocytic leukemia protein (PML), thus killing the leukemia stem cells (LSCs). Arsenic Trioxide 0-3 PML nuclear body scaffold Homo sapiens 90-120 30763586-4 2019 ATO acts through a direct arsenic binding to cysteine residues in zinc fingers located in promyelocytic leukemia protein (PML), thus killing the leukemia stem cells (LSCs). Arsenic Trioxide 0-3 PML nuclear body scaffold Homo sapiens 122-125 30693698-3 2018 As2O3 is currently used as the first-line drug for patients with APL, and the mechanism may be:As2O3 directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 119-122 30693698-3 2018 As2O3 is currently used as the first-line drug for patients with APL, and the mechanism may be:As2O3 directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 255-258 30693698-3 2018 As2O3 is currently used as the first-line drug for patients with APL, and the mechanism may be:As2O3 directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 255-258 30693698-3 2018 As2O3 is currently used as the first-line drug for patients with APL, and the mechanism may be:As2O3 directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Arsenic Trioxide 95-100 PML nuclear body scaffold Homo sapiens 119-122 30693698-3 2018 As2O3 is currently used as the first-line drug for patients with APL, and the mechanism may be:As2O3 directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Arsenic Trioxide 95-100 PML nuclear body scaffold Homo sapiens 255-258 30693698-3 2018 As2O3 is currently used as the first-line drug for patients with APL, and the mechanism may be:As2O3 directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Arsenic Trioxide 95-100 PML nuclear body scaffold Homo sapiens 255-258 30693698-5 2018 In this review, we discuss the structure and function of PML proteins; the pathogenesis of APL induced by P/R fusion protein; the involvement of PML protein in treatment of APL patient with As2O3; and explain how PML protein mutations could cause resistance to As2O3 therapy. Arsenic Trioxide 190-195 PML nuclear body scaffold Homo sapiens 145-148 30693698-5 2018 In this review, we discuss the structure and function of PML proteins; the pathogenesis of APL induced by P/R fusion protein; the involvement of PML protein in treatment of APL patient with As2O3; and explain how PML protein mutations could cause resistance to As2O3 therapy. Arsenic Trioxide 190-195 PML nuclear body scaffold Homo sapiens 145-148 30693698-5 2018 In this review, we discuss the structure and function of PML proteins; the pathogenesis of APL induced by P/R fusion protein; the involvement of PML protein in treatment of APL patient with As2O3; and explain how PML protein mutations could cause resistance to As2O3 therapy. Arsenic Trioxide 261-266 PML nuclear body scaffold Homo sapiens 145-148 30693698-5 2018 In this review, we discuss the structure and function of PML proteins; the pathogenesis of APL induced by P/R fusion protein; the involvement of PML protein in treatment of APL patient with As2O3; and explain how PML protein mutations could cause resistance to As2O3 therapy. Arsenic Trioxide 261-266 PML nuclear body scaffold Homo sapiens 145-148 29596829-5 2018 Recent studies suggest that pharmacological concentrations of the APL therapeutic drugs, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), affect post-mitotic nuclear import of the APL-associated oncoprotein PML/RARA. Arsenic Trioxide 142-145 PML nuclear body scaffold Homo sapiens 217-220 28521962-6 2018 All-trans retinoic acid and arsenic trioxide treatment has been implemented for promyelocytic leukemia to target the PML-RARalpha fusion protein. Arsenic Trioxide 28-44 PML nuclear body scaffold Homo sapiens 117-120 29387217-1 2018 Acute promyelocytic leukemia (APL), characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid alpha receptor (RARalpha) fusion protein, responds to treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 220-236 PML nuclear body scaffold Homo sapiens 97-100 29387217-1 2018 Acute promyelocytic leukemia (APL), characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid alpha receptor (RARalpha) fusion protein, responds to treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 238-241 PML nuclear body scaffold Homo sapiens 97-100 28712407-5 2017 Compared with control group without medication, the PML protein expression of APL cells in initial onset cases had larger fluorescent signals in the ATRA group, As2O3 group and As4S4 group, whereas there were no significant changes in the arabinoside cytosine group and the homoharringtonine group. Arsenic Trioxide 161-166 PML nuclear body scaffold Homo sapiens 52-55 28525371-0 2017 Arsenic trioxide and angiotensin II have inhibitory effects on HERG protein expression: Evidence for the role of PML SUMOylation. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 113-116 28525371-3 2017 Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Arsenic Trioxide 5-21 PML nuclear body scaffold Homo sapiens 137-140 28525371-3 2017 Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Arsenic Trioxide 5-21 PML nuclear body scaffold Homo sapiens 187-190 28525371-3 2017 Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Arsenic Trioxide 23-26 PML nuclear body scaffold Homo sapiens 137-140 28525371-3 2017 Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Arsenic Trioxide 23-26 PML nuclear body scaffold Homo sapiens 187-190 29973452-2 2018 The advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as molecular targeted therapies directed against PML-RARalpha has been a major breakthrough in APL treatment. Arsenic Trioxide 49-65 PML nuclear body scaffold Homo sapiens 121-124 29973452-2 2018 The advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as molecular targeted therapies directed against PML-RARalpha has been a major breakthrough in APL treatment. Arsenic Trioxide 67-70 PML nuclear body scaffold Homo sapiens 121-124 28695742-8 2017 More interestingly, after treating cells with arsenic trioxide (As2O3), the number of PML-NBs is no longer reduced when the non-SUMOylated triple mutant Ki-1/57 is expressed, suggesting that the SUMOylation of Ki-1/57 has a role in the control of As2O3-induced PML-NB formation. Arsenic Trioxide 46-62 PML nuclear body scaffold Homo sapiens 86-89 28695742-8 2017 More interestingly, after treating cells with arsenic trioxide (As2O3), the number of PML-NBs is no longer reduced when the non-SUMOylated triple mutant Ki-1/57 is expressed, suggesting that the SUMOylation of Ki-1/57 has a role in the control of As2O3-induced PML-NB formation. Arsenic Trioxide 64-69 PML nuclear body scaffold Homo sapiens 86-89 28712407-7 2017 Also, As2O3 and As4S4 turned the PML protein expression of NB4 and MR2 cells from small fluorescent signals into large ones. Arsenic Trioxide 6-11 PML nuclear body scaffold Homo sapiens 33-36 28239645-3 2017 Here, we find that the promyelocytic leukemia protein PML exerts a prometastatic function in TNBC that can be targeted by arsenic trioxide. Arsenic Trioxide 122-138 PML nuclear body scaffold Homo sapiens 54-57 28656178-10 2017 The presence of PML was not required for the restriction of nonhuman retroviruses by TRIM5alpha (another human TRIM protein), and TRIM5alpha was inhibited by arsenic trioxide through a PML-independent mechanism. Arsenic Trioxide 158-174 PML nuclear body scaffold Homo sapiens 185-188 28492552-1 2017 All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL) cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha). Arsenic Trioxide 38-54 PML nuclear body scaffold Homo sapiens 243-246 28492552-1 2017 All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL) cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha). Arsenic Trioxide 56-59 PML nuclear body scaffold Homo sapiens 243-246 28492552-2 2017 Yet, ~10-15% of APL patients are not cured by ATRA- and ATO-based therapies, and a potential failure of ATRA and ATO in completely reversing PML/RARalpha-driven oncogenic alterations has not been comprehensively examined. Arsenic Trioxide 113-116 PML nuclear body scaffold Homo sapiens 141-144 28492552-5 2017 Irf8, whose expression increased along with spontaneous differentiation of the APL progenitors in vivo, represented such a PML/RARalpha-dysregulated gene that was refractory to ATRA/ATO signaling. Arsenic Trioxide 182-185 PML nuclear body scaffold Homo sapiens 123-126 28028657-0 2017 PML-RARA mutations confer varying arsenic trioxide resistance. Arsenic Trioxide 34-50 PML nuclear body scaffold Homo sapiens 0-3 28486108-6 2017 Genetically inhibiting TRIB3 expression or combination of a peptide disturbing TRIB3/PML-RARalpha interaction with ATRA/As2O3 eradicates APL by accelerating PML-RARalpha degradation. Arsenic Trioxide 120-125 PML nuclear body scaffold Homo sapiens 85-88 28486108-6 2017 Genetically inhibiting TRIB3 expression or combination of a peptide disturbing TRIB3/PML-RARalpha interaction with ATRA/As2O3 eradicates APL by accelerating PML-RARalpha degradation. Arsenic Trioxide 120-125 PML nuclear body scaffold Homo sapiens 157-160 28239645-8 2017 Notably, pharmacological inhibition of PML with arsenic trioxide, a PML-degrading agent used to treat promyelocytic leukemia patients, delays tumor growth, impairs TNBC metastasis, and cooperates with chemotherapy by preventing metastatic dissemination. Arsenic Trioxide 48-64 PML nuclear body scaffold Homo sapiens 39-42 28239645-8 2017 Notably, pharmacological inhibition of PML with arsenic trioxide, a PML-degrading agent used to treat promyelocytic leukemia patients, delays tumor growth, impairs TNBC metastasis, and cooperates with chemotherapy by preventing metastatic dissemination. Arsenic Trioxide 48-64 PML nuclear body scaffold Homo sapiens 68-71 28129653-2 2017 All-trans retinoic acid (ATRA) and arsenic trioxide cure most patients by directly targeting PML-RARalpha. Arsenic Trioxide 35-51 PML nuclear body scaffold Homo sapiens 93-96 27903803-9 2017 This is strengthened by the fact that IE1 also prevents As2O3-mediated hyperSUMOylation of K160, thereby blocking PML degradation. Arsenic Trioxide 56-61 PML nuclear body scaffold Homo sapiens 114-117 26728337-2 2016 PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). Arsenic Trioxide 62-78 PML nuclear body scaffold Homo sapiens 0-3 28125064-2 2017 However, it has been reported that As2O3 resistant patients are frequently found in relapsed APL after consolidation therapy, which is due to the point mutations in B-box type 2 motifs of promyelocytic leukemia (PML) gene. Arsenic Trioxide 35-40 PML nuclear body scaffold Homo sapiens 188-210 28125064-2 2017 However, it has been reported that As2O3 resistant patients are frequently found in relapsed APL after consolidation therapy, which is due to the point mutations in B-box type 2 motifs of promyelocytic leukemia (PML) gene. Arsenic Trioxide 35-40 PML nuclear body scaffold Homo sapiens 212-215 27133819-0 2016 PML-RARalpha kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy. Arsenic Trioxide 126-129 PML nuclear body scaffold Homo sapiens 0-3 27030546-0 2016 PCGF2 negatively regulates arsenic trioxide-induced PML-RARA protein degradation via UBE2I inhibition in NB4 cells. Arsenic Trioxide 27-43 PML nuclear body scaffold Homo sapiens 52-55 27030546-1 2016 Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated sumoylation. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 99-102 27030546-1 2016 Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated sumoylation. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 99-102 27030546-3 2016 Thus, we hypothesized that PCGF2 might play a role in ATO-induced PML-RARA degradation by interacting with UBE2I. Arsenic Trioxide 54-57 PML nuclear body scaffold Homo sapiens 66-69 27030546-6 2016 Moreover, overexpression of PCGF2 protected ATO-mediated degradation of ectopic and endogenous PML-RARA in 293T and NB4 cells, respectively. Arsenic Trioxide 44-47 PML nuclear body scaffold Homo sapiens 95-98 27030546-10 2016 Intriguingly, upon ATO-treatment, such interaction was disrupted and UBE2I was co-immunoprecipitated or co-localized with its SUMO substrate, PML-RARA. Arsenic Trioxide 19-22 PML nuclear body scaffold Homo sapiens 142-145 27030546-11 2016 Taken together, our results suggested a novel role of PCGF2 in ATO-mediated degradation of PML-RARA that PCGF2 might act as a negative regulator of UBE2I via direct interaction. Arsenic Trioxide 63-66 PML nuclear body scaffold Homo sapiens 91-94 26728337-2 2016 PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). Arsenic Trioxide 80-83 PML nuclear body scaffold Homo sapiens 0-3 26728337-3 2016 We analysed the prevalence of PML mutations in 32 patients with de novo or therapy-related APL (t-APL; n = 5), treated with ATO. Arsenic Trioxide 124-127 PML nuclear body scaffold Homo sapiens 30-33 26537301-0 2016 Varying responses of PML-RARA with different genetic mutations to arsenic trioxide. Arsenic Trioxide 66-82 PML nuclear body scaffold Homo sapiens 21-24 26537301-4 2016 Here we performed in vitro functional analyses and a retrospective analysis of APL patients to investigate the effect of PML-RARA mutations in mediating resistance to arsenic trioxide. Arsenic Trioxide 167-183 PML nuclear body scaffold Homo sapiens 121-124 26060329-5 2015 We hypothesized that constitutive SUMO2 conjugation and deconjugation occurred basally and that arsenic trioxide treatment caused the exchange of SUMO2 for SUMO1 on a fraction of Lys(65) in PML. Arsenic Trioxide 96-112 PML nuclear body scaffold Homo sapiens 190-193 26294332-8 2015 The PML-region mutations were associated with response to ATO-based therapy (P < 0.0001), number of relapses (P = 0.001), and early relapse (P = 0.013). Arsenic Trioxide 58-61 PML nuclear body scaffold Homo sapiens 4-7 26294332-10 2015 This study demonstrated frequent mutations of PML-RARA and supported a clonal selection model in relation to APL relapse and ATO resistance. Arsenic Trioxide 125-128 PML nuclear body scaffold Homo sapiens 46-49 26118777-0 2015 Promyelocytic leukemia protein induces arsenic trioxide resistance through regulation of aldehyde dehydrogenase 3 family member A1 in hepatocellular carcinoma. Arsenic Trioxide 39-55 PML nuclear body scaffold Homo sapiens 0-30 26118777-2 2015 Promyelocytic leukemia protein (PML) is central to ATO treatment efficacy of acute promyelocytic leukemia. Arsenic Trioxide 51-54 PML nuclear body scaffold Homo sapiens 0-30 26118777-2 2015 Promyelocytic leukemia protein (PML) is central to ATO treatment efficacy of acute promyelocytic leukemia. Arsenic Trioxide 51-54 PML nuclear body scaffold Homo sapiens 32-35 26118777-3 2015 We examine impacts of PML expression on the effectiveness of ATO treatment in HCC. Arsenic Trioxide 61-64 PML nuclear body scaffold Homo sapiens 22-25 26118777-5 2015 However, high PML expression dampens the anti-tumor effects of ATO in HCC cells. Arsenic Trioxide 63-66 PML nuclear body scaffold Homo sapiens 14-17 26118777-9 2015 Clinically, ATO treatment decreases the disease progression rate in advanced HCC patients with negative PML expression. Arsenic Trioxide 12-15 PML nuclear body scaffold Homo sapiens 104-107 26118777-10 2015 In conclusion, PML confers a favorable prognosis in HCC patients, but it induces ATO resistance through ALDH3A1 up-regulation in HCC cells. Arsenic Trioxide 81-84 PML nuclear body scaffold Homo sapiens 15-18 26118777-11 2015 ATO is effective for HCC patients with negative PML expression. Arsenic Trioxide 0-3 PML nuclear body scaffold Homo sapiens 48-51 26118777-12 2015 Combined with an ALDH3A1 inhibitor, ATO may be efficacious in patients with positive PML expression. Arsenic Trioxide 36-39 PML nuclear body scaffold Homo sapiens 85-88 26058416-4 2015 It has been found that all-trans-retinoic acid (ATRA) or arsenic trioxide (ATO) alone exerts therapeutic effect on APL patients with the PML-RARalpha fusion gene, and the combination of both drugs can act synergistically to further enhance the cure rate of the patients. Arsenic Trioxide 57-73 PML nuclear body scaffold Homo sapiens 137-140 26058416-4 2015 It has been found that all-trans-retinoic acid (ATRA) or arsenic trioxide (ATO) alone exerts therapeutic effect on APL patients with the PML-RARalpha fusion gene, and the combination of both drugs can act synergistically to further enhance the cure rate of the patients. Arsenic Trioxide 75-78 PML nuclear body scaffold Homo sapiens 137-140 26213848-2 2015 The probable explanation for As2O3-induced cell differentiation is the direct targeting of PML-RARalpha oncoprotein by As2O3, which results in initiation of PML-RARalpha degradation. Arsenic Trioxide 29-34 PML nuclear body scaffold Homo sapiens 91-94 26213848-2 2015 The probable explanation for As2O3-induced cell differentiation is the direct targeting of PML-RARalpha oncoprotein by As2O3, which results in initiation of PML-RARalpha degradation. Arsenic Trioxide 29-34 PML nuclear body scaffold Homo sapiens 157-160 26213848-2 2015 The probable explanation for As2O3-induced cell differentiation is the direct targeting of PML-RARalpha oncoprotein by As2O3, which results in initiation of PML-RARalpha degradation. Arsenic Trioxide 119-124 PML nuclear body scaffold Homo sapiens 91-94 26213848-2 2015 The probable explanation for As2O3-induced cell differentiation is the direct targeting of PML-RARalpha oncoprotein by As2O3, which results in initiation of PML-RARalpha degradation. Arsenic Trioxide 119-124 PML nuclear body scaffold Homo sapiens 157-160 26060329-2 2015 Arsenic trioxide chemotherapy of this cancer induces the PML moiety to organize nuclear bodies, where the oncoprotein is degraded. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 57-60 25795919-2 2015 Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Arsenic Trioxide 161-177 PML nuclear body scaffold Homo sapiens 227-230 25795919-2 2015 Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Arsenic Trioxide 179-182 PML nuclear body scaffold Homo sapiens 227-230 25795919-7 2015 Interestingly, similarly to what was described for PML, oxidative stress also mediates ATO-induced degradation of the NPM1 mutant oncoprotein. Arsenic Trioxide 87-90 PML nuclear body scaffold Homo sapiens 51-54 25759405-1 2015 The majority of patients with acute promyelocytic leukaemia (APL) carry the hallmark t(15;17)(q22;q21) translocation, involving the promyelocytic leukaemia/retinoic acid receptor-alpha (PML/RARalpha) fusion gene, and by sensitivity of blast cells to all-trans retinoic acid (ATRA) and/or arsenic trioxide therapy. Arsenic Trioxide 288-304 PML nuclear body scaffold Homo sapiens 186-189 27182481-4 2015 The identification of arsenic trioxide (ATO) as a valid therapy not only in relapsed patients but also as an alternative to standard therapy alone or in association with all-trans-retinoic acid enlarges the setting of validation of MRD evaluation in APL patients, considering a possible different clearance of PML-RARalpha with innovative therapy different from the standard ones. Arsenic Trioxide 40-43 PML nuclear body scaffold Homo sapiens 310-313 26517826-2 2015 Arsenic trioxide (ATO) upregulates expression of TGF-beta1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 131-134 26517826-2 2015 Arsenic trioxide (ATO) upregulates expression of TGF-beta1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. Arsenic Trioxide 109-112 PML nuclear body scaffold Homo sapiens 131-134 27182481-4 2015 The identification of arsenic trioxide (ATO) as a valid therapy not only in relapsed patients but also as an alternative to standard therapy alone or in association with all-trans-retinoic acid enlarges the setting of validation of MRD evaluation in APL patients, considering a possible different clearance of PML-RARalpha with innovative therapy different from the standard ones. Arsenic Trioxide 22-38 PML nuclear body scaffold Homo sapiens 310-313 23680002-2 2013 Here we show that co-administration of GCV and arsenic trioxide (ATO), a PML NB disruptor, reduces tumor volume in a xenograft model of nasopharyngeal carcinoma utilizing CNE1 cells. Arsenic Trioxide 47-63 PML nuclear body scaffold Homo sapiens 73-76 25319615-5 2014 On the other hand, arsenic trioxide (ATO), another promising agent used to treat APL, directly binds to the PML moiety of the PML-RARalpha protein, causing oxidation and multimerization. Arsenic Trioxide 19-35 PML nuclear body scaffold Homo sapiens 108-111 25319615-5 2014 On the other hand, arsenic trioxide (ATO), another promising agent used to treat APL, directly binds to the PML moiety of the PML-RARalpha protein, causing oxidation and multimerization. Arsenic Trioxide 19-35 PML nuclear body scaffold Homo sapiens 126-129 25319615-5 2014 On the other hand, arsenic trioxide (ATO), another promising agent used to treat APL, directly binds to the PML moiety of the PML-RARalpha protein, causing oxidation and multimerization. Arsenic Trioxide 37-40 PML nuclear body scaffold Homo sapiens 108-111 25319615-5 2014 On the other hand, arsenic trioxide (ATO), another promising agent used to treat APL, directly binds to the PML moiety of the PML-RARalpha protein, causing oxidation and multimerization. Arsenic Trioxide 37-40 PML nuclear body scaffold Homo sapiens 126-129 24164099-3 2013 The basic mechanism through which As2O3 induces molecular remission in APL patients include direct targeting of PML and retinoic acid receptor alpha fusion protein (PML-RARalpha) by arsenic resulting in oncoprotein degradation leading to partial differentiation. Arsenic Trioxide 34-39 PML nuclear body scaffold Homo sapiens 112-115 24164099-3 2013 The basic mechanism through which As2O3 induces molecular remission in APL patients include direct targeting of PML and retinoic acid receptor alpha fusion protein (PML-RARalpha) by arsenic resulting in oncoprotein degradation leading to partial differentiation. Arsenic Trioxide 34-39 PML nuclear body scaffold Homo sapiens 165-168 23734343-2 2013 Treatment of APL patients with arsenic trioxide (As2O3) reverses the disease phenotype by a process involving the degradation of the fusion protein via its PML moiety. Arsenic Trioxide 31-47 PML nuclear body scaffold Homo sapiens 156-159 23734343-2 2013 Treatment of APL patients with arsenic trioxide (As2O3) reverses the disease phenotype by a process involving the degradation of the fusion protein via its PML moiety. Arsenic Trioxide 49-54 PML nuclear body scaffold Homo sapiens 156-159 23734343-8 2013 Finally, the key players involved in the degradation of the PML isoforms in response to As2O3 or other inducers are discussed. Arsenic Trioxide 88-93 PML nuclear body scaffold Homo sapiens 60-63 24907012-6 2014 More recently, arsenic trioxide (ATO) has been shown to contribute degradation of the PML-RARalpha oncoprotein through bonding the PML moiety and has shown excellent synergism with ATRA in clinical trials. Arsenic Trioxide 15-31 PML nuclear body scaffold Homo sapiens 86-89 24907012-6 2014 More recently, arsenic trioxide (ATO) has been shown to contribute degradation of the PML-RARalpha oncoprotein through bonding the PML moiety and has shown excellent synergism with ATRA in clinical trials. Arsenic Trioxide 15-31 PML nuclear body scaffold Homo sapiens 131-134 24907012-6 2014 More recently, arsenic trioxide (ATO) has been shown to contribute degradation of the PML-RARalpha oncoprotein through bonding the PML moiety and has shown excellent synergism with ATRA in clinical trials. Arsenic Trioxide 33-36 PML nuclear body scaffold Homo sapiens 86-89 24907012-6 2014 More recently, arsenic trioxide (ATO) has been shown to contribute degradation of the PML-RARalpha oncoprotein through bonding the PML moiety and has shown excellent synergism with ATRA in clinical trials. Arsenic Trioxide 33-36 PML nuclear body scaffold Homo sapiens 131-134 24344243-3 2013 The empirical discoveries that PML-RARa-associated APL is sensitive to both all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), and the subsequent understanding of the mechanisms of action of these drugs, have led to efforts to understand the contribution of molecular events to APL cell differentiation, leukemia-initiating cell (LIC) clearance, and disease eradication in vitro and in vivo. Arsenic Trioxide 111-127 PML nuclear body scaffold Homo sapiens 31-34 24344243-3 2013 The empirical discoveries that PML-RARa-associated APL is sensitive to both all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), and the subsequent understanding of the mechanisms of action of these drugs, have led to efforts to understand the contribution of molecular events to APL cell differentiation, leukemia-initiating cell (LIC) clearance, and disease eradication in vitro and in vivo. Arsenic Trioxide 129-132 PML nuclear body scaffold Homo sapiens 31-34 23208507-2 2013 In APL cells with PML/RARA fusions, arsenic trioxide and all-trans retinoic acid treatments specifically target the fusion protein for proteasome-dependent degradation, thereby promoting cellular differentiation and clinical remission of disease. Arsenic Trioxide 36-52 PML nuclear body scaffold Homo sapiens 18-21 23670176-3 2013 Genetic mutations resulting in amino acid substitution in the retinoic acid receptor alpha (RARalpha) ligand binding domain (LBD) and the PML-B2 domain of PML-RARalpha, respectively, have been reported as molecular mechanisms underlying resistance to ATRA and As2O3. Arsenic Trioxide 260-265 PML nuclear body scaffold Homo sapiens 138-141 23670176-3 2013 Genetic mutations resulting in amino acid substitution in the retinoic acid receptor alpha (RARalpha) ligand binding domain (LBD) and the PML-B2 domain of PML-RARalpha, respectively, have been reported as molecular mechanisms underlying resistance to ATRA and As2O3. Arsenic Trioxide 260-265 PML nuclear body scaffold Homo sapiens 155-158 23670176-5 2013 The PML-B2 mutation interferes with the direct binding of As2O3 with PML-B2, and PML-RARalpha SUMOylation with As2O3 followed by multimerization and degradation is impaired. Arsenic Trioxide 58-63 PML nuclear body scaffold Homo sapiens 4-7 23670176-5 2013 The PML-B2 mutation interferes with the direct binding of As2O3 with PML-B2, and PML-RARalpha SUMOylation with As2O3 followed by multimerization and degradation is impaired. Arsenic Trioxide 58-63 PML nuclear body scaffold Homo sapiens 69-72 23670176-5 2013 The PML-B2 mutation interferes with the direct binding of As2O3 with PML-B2, and PML-RARalpha SUMOylation with As2O3 followed by multimerization and degradation is impaired. Arsenic Trioxide 58-63 PML nuclear body scaffold Homo sapiens 69-72 23680002-2 2013 Here we show that co-administration of GCV and arsenic trioxide (ATO), a PML NB disruptor, reduces tumor volume in a xenograft model of nasopharyngeal carcinoma utilizing CNE1 cells. Arsenic Trioxide 65-68 PML nuclear body scaffold Homo sapiens 73-76 22406621-5 2012 In addition, PIAS1-mediated SUMOylation of PML-RARA was essential for induction of its degradation by arsenic trioxide, an effective APL treatment. Arsenic Trioxide 102-118 PML nuclear body scaffold Homo sapiens 43-46 22692509-5 2012 This block in PML body recycling is readily detected at pharmacologic relevant ATO concentrations (0.02-0.5muM) that do not cause detectable cell-cycle defects, and it does not require modification of PML by SUMOylation. Arsenic Trioxide 79-82 PML nuclear body scaffold Homo sapiens 14-17 22692509-7 2012 Thus, ATO may inhibit nuclear activities of PML and PML/RARA in postmitotic cells through CyPN-dependent cytoplasmic sequestration. Arsenic Trioxide 6-9 PML nuclear body scaffold Homo sapiens 44-47 22692509-7 2012 Thus, ATO may inhibit nuclear activities of PML and PML/RARA in postmitotic cells through CyPN-dependent cytoplasmic sequestration. Arsenic Trioxide 6-9 PML nuclear body scaffold Homo sapiens 52-55 23430110-10 2013 In addition, downregulation of PML by arsenic trioxide suppressed monosodium urate (MSU)-induced IL-1beta production, suggesting that targeting to PML could be used to treat NLRP3 inflammasome-associated diseases. Arsenic Trioxide 38-54 PML nuclear body scaffold Homo sapiens 31-34 23430110-10 2013 In addition, downregulation of PML by arsenic trioxide suppressed monosodium urate (MSU)-induced IL-1beta production, suggesting that targeting to PML could be used to treat NLRP3 inflammasome-associated diseases. Arsenic Trioxide 38-54 PML nuclear body scaffold Homo sapiens 147-150 23469683-9 2013 ATO caused a profound decrease in the protein level of PML/RARalpha in NB4 cells after 48 h, but there was no change with AICAR and the combination. Arsenic Trioxide 0-3 PML nuclear body scaffold Homo sapiens 55-58 24356076-10 2013 As2O3 induced degradation of promyelocytic leukemia (PML), and then induced the down-regulation of both let-7d and miR-766 in NB4 cells. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 53-56 22692509-3 2012 Here we investigated the fate of PML-generated nuclear structures called PML bodies in ATO-treated cells. Arsenic Trioxide 87-90 PML nuclear body scaffold Homo sapiens 33-36 22692509-3 2012 Here we investigated the fate of PML-generated nuclear structures called PML bodies in ATO-treated cells. Arsenic Trioxide 87-90 PML nuclear body scaffold Homo sapiens 73-76 22362285-2 2012 Arsenic trioxide (As(2)O(3)) is known to degrade PML protein and has been used for the treatment of patients with acute PML. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 49-52 22362285-2 2012 Arsenic trioxide (As(2)O(3)) is known to degrade PML protein and has been used for the treatment of patients with acute PML. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 120-123 21975125-5 2011 Disruption of PML NBs with arsenic trioxide or a PML siRNA restores reporter activity. Arsenic Trioxide 27-43 PML nuclear body scaffold Homo sapiens 14-17 22056243-0 2012 Curing APL through PML/RARA degradation by As2O3. Arsenic Trioxide 43-48 PML nuclear body scaffold Homo sapiens 19-22 22056243-6 2012 As discussed below, arsenic binding, oxidation, sumoylation on PML nuclear bodies, and RNF4-mediated ubiquitination all contribute to the As(2)O(3)-triggered catabolism of PML/RARA. Arsenic Trioxide 138-147 PML nuclear body scaffold Homo sapiens 63-66 22056243-6 2012 As discussed below, arsenic binding, oxidation, sumoylation on PML nuclear bodies, and RNF4-mediated ubiquitination all contribute to the As(2)O(3)-triggered catabolism of PML/RARA. Arsenic Trioxide 138-147 PML nuclear body scaffold Homo sapiens 172-175 23028697-0 2012 Requirement of PML SUMO interacting motif for RNF4- or arsenic trioxide-induced degradation of nuclear PML isoforms. Arsenic Trioxide 55-71 PML nuclear body scaffold Homo sapiens 15-18 23028697-0 2012 Requirement of PML SUMO interacting motif for RNF4- or arsenic trioxide-induced degradation of nuclear PML isoforms. Arsenic Trioxide 55-71 PML nuclear body scaffold Homo sapiens 103-106 23028697-4 2012 Arsenic trioxide (As2O3) enhances PML SUMOylation leading to an increase in PML NB size and promotes its interaction with RNF4, a poly-SUMO-dependent ubiquitin E3 ligase responsible for proteasome-mediated PML degradation. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 34-37 23028697-4 2012 Arsenic trioxide (As2O3) enhances PML SUMOylation leading to an increase in PML NB size and promotes its interaction with RNF4, a poly-SUMO-dependent ubiquitin E3 ligase responsible for proteasome-mediated PML degradation. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 76-79 23028697-4 2012 Arsenic trioxide (As2O3) enhances PML SUMOylation leading to an increase in PML NB size and promotes its interaction with RNF4, a poly-SUMO-dependent ubiquitin E3 ligase responsible for proteasome-mediated PML degradation. Arsenic Trioxide 18-23 PML nuclear body scaffold Homo sapiens 34-37 23028697-4 2012 Arsenic trioxide (As2O3) enhances PML SUMOylation leading to an increase in PML NB size and promotes its interaction with RNF4, a poly-SUMO-dependent ubiquitin E3 ligase responsible for proteasome-mediated PML degradation. Arsenic Trioxide 18-23 PML nuclear body scaffold Homo sapiens 76-79 23028697-7 2012 Using a bioluminescence resonance energy transfer (BRET) assay in living cells, we found that As2O3 enhanced the SUMOylation and interaction with RNF4 of nuclear PML isoforms (I to VI). Arsenic Trioxide 94-99 PML nuclear body scaffold Homo sapiens 162-165 23028697-8 2012 In addition, among the nuclear PML isoforms, only the one lacking the SIM sequence, PMLVI, was resistant to As2O3-induced PML degradation. Arsenic Trioxide 108-113 PML nuclear body scaffold Homo sapiens 31-34 23028697-8 2012 In addition, among the nuclear PML isoforms, only the one lacking the SIM sequence, PMLVI, was resistant to As2O3-induced PML degradation. Arsenic Trioxide 108-113 PML nuclear body scaffold Homo sapiens 84-87 23028697-13 2012 Our results demonstrate that the SIM of PML is dispensable for PML SUMOylation and interaction with RNF4 but is required for efficient PML ubiquitination, recruitment of proteasome components within NBs and proteasome-dependent degradation of PML in response to As2O3. Arsenic Trioxide 262-267 PML nuclear body scaffold Homo sapiens 40-43 21454520-3 2011 Arsenic trioxide, a drug for patients with acute promyelocytic leukemia, is found to target and degrade a class of proteins with high levels of cysteine residues and vicinal thiol groups, such as promyelocytic leukemia protein (PML) and PML-retinoic acid receptor alpha fusion protein. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 196-226 22040992-2 2011 As a subtype of acute myeloid leukemia, acute promyelocytic leukemia (APL) represents the target of therapy due to the good response of the oncogenic protein PML-RARalpha to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 209-225 PML nuclear body scaffold Homo sapiens 158-161 22040992-2 2011 As a subtype of acute myeloid leukemia, acute promyelocytic leukemia (APL) represents the target of therapy due to the good response of the oncogenic protein PML-RARalpha to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Arsenic Trioxide 227-230 PML nuclear body scaffold Homo sapiens 158-161 21613260-0 2011 Missense mutations in PML-RARA are critical for the lack of responsiveness to arsenic trioxide treatment. Arsenic Trioxide 78-94 PML nuclear body scaffold Homo sapiens 22-25 21613260-4 2011 When wild-type or mutated PML-RARA (PR-WT and PR-B/L-mut, respectively) were overexpressed in HeLa cells, immunoblotting showed SUMOylated and/or oligomerized protein bands in PR-WT but not in PR-B/L-mut after As2O3 treatment. Arsenic Trioxide 210-215 PML nuclear body scaffold Homo sapiens 26-29 21454520-3 2011 Arsenic trioxide, a drug for patients with acute promyelocytic leukemia, is found to target and degrade a class of proteins with high levels of cysteine residues and vicinal thiol groups, such as promyelocytic leukemia protein (PML) and PML-retinoic acid receptor alpha fusion protein. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 228-231 21454520-3 2011 Arsenic trioxide, a drug for patients with acute promyelocytic leukemia, is found to target and degrade a class of proteins with high levels of cysteine residues and vicinal thiol groups, such as promyelocytic leukemia protein (PML) and PML-retinoic acid receptor alpha fusion protein. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 237-240 21217775-10 2011 These data suggest the possible involvement of this fusion protein in the leukemogenesis of B-ALL in a dual dominant-negative manner and the possibility that ALL with PAX5-PML can be treated with ATO. Arsenic Trioxide 196-199 PML nuclear body scaffold Homo sapiens 172-175 21217775-9 2011 Furthermore, treatment with arsenic trioxide (ATO) induced PML sumoylation and reconstitution of PML NBs, and overcame the anti-apoptotic effect of PAX5-PML in HeLa cells. Arsenic Trioxide 28-44 PML nuclear body scaffold Homo sapiens 59-62 21217775-9 2011 Furthermore, treatment with arsenic trioxide (ATO) induced PML sumoylation and reconstitution of PML NBs, and overcame the anti-apoptotic effect of PAX5-PML in HeLa cells. Arsenic Trioxide 28-44 PML nuclear body scaffold Homo sapiens 97-100 21217775-9 2011 Furthermore, treatment with arsenic trioxide (ATO) induced PML sumoylation and reconstitution of PML NBs, and overcame the anti-apoptotic effect of PAX5-PML in HeLa cells. Arsenic Trioxide 28-44 PML nuclear body scaffold Homo sapiens 97-100 21217775-9 2011 Furthermore, treatment with arsenic trioxide (ATO) induced PML sumoylation and reconstitution of PML NBs, and overcame the anti-apoptotic effect of PAX5-PML in HeLa cells. Arsenic Trioxide 46-49 PML nuclear body scaffold Homo sapiens 59-62 21217775-9 2011 Furthermore, treatment with arsenic trioxide (ATO) induced PML sumoylation and reconstitution of PML NBs, and overcame the anti-apoptotic effect of PAX5-PML in HeLa cells. Arsenic Trioxide 46-49 PML nuclear body scaffold Homo sapiens 97-100 21217775-9 2011 Furthermore, treatment with arsenic trioxide (ATO) induced PML sumoylation and reconstitution of PML NBs, and overcame the anti-apoptotic effect of PAX5-PML in HeLa cells. Arsenic Trioxide 46-49 PML nuclear body scaffold Homo sapiens 97-100 20699661-2 2010 Arsenic trioxide (As(2)O(3)), used in the treatment of promyelocytic leukemia (PML), triggers cell death in several solid tumor cell lines including ovarian carcinomas. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 79-82 20528759-4 2010 All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which are the major molecularly targeted therapies in APL, affect the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. Arsenic Trioxide 35-51 PML nuclear body scaffold Homo sapiens 129-132 20528759-4 2010 All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which are the major molecularly targeted therapies in APL, affect the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. Arsenic Trioxide 53-56 PML nuclear body scaffold Homo sapiens 129-132 20378816-2 2010 Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 141-144 20574048-1 2010 Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid and/or arsenic trioxide represents a paradigm in targeted cancer therapy because these drugs cause clinical remission by affecting the stability of the fusion oncoprotein promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARA). Arsenic Trioxide 84-100 PML nuclear body scaffold Homo sapiens 272-275 20574048-4 2010 We found that both all-trans retinoic acid and arsenic trioxide induce autophagy via the mammalian target of rapamycin pathway in APL cells and that autophagic degradation contributes significantly both to the basal turnover as well as the therapy-induced proteolysis of PML/RARA. Arsenic Trioxide 47-63 PML nuclear body scaffold Homo sapiens 271-274 20615082-8 2010 In summary, our results indicate that ATO in conjunction with ATRA is of potential chemotherapeutic use in PML-RARalpha negative leukemias. Arsenic Trioxide 38-41 PML nuclear body scaffold Homo sapiens 107-110 20609355-0 2010 PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3. Arsenic Trioxide 77-82 PML nuclear body scaffold Homo sapiens 0-3 20615082-0 2010 Arsenic trioxide cooperates with all trans retinoic acid to enhance mitogen-activated protein kinase activation and differentiation in PML-RARalpha negative human myeloblastic leukemia cells. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 135-138 20615082-1 2010 Arsenic trioxide (ATO) synergistically promotes all trans retinoic acid (ATRA)-induced differentiation of PML-RARalpha negative HL-60 myeloblastic leukemia cells. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 106-109 20615082-1 2010 Arsenic trioxide (ATO) synergistically promotes all trans retinoic acid (ATRA)-induced differentiation of PML-RARalpha negative HL-60 myeloblastic leukemia cells. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 106-109 20615082-2 2010 In PML-RARalpha positive myeloid leukemia cells, ATO is known to cause degradation of PML-RARalpha with subsequent induced myeloid differentiation. Arsenic Trioxide 49-52 PML nuclear body scaffold Homo sapiens 3-6 19468689-1 2010 Arsenic trioxide (ATO) is an inorganic arsenic derivative that is highly effective against PML-RARalpha-positive leukemia but much less against other hematological malignancies. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 91-94 19468689-1 2010 Arsenic trioxide (ATO) is an inorganic arsenic derivative that is highly effective against PML-RARalpha-positive leukemia but much less against other hematological malignancies. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 91-94 20455087-3 2010 Both retinoic acid (RA) and arsenic trioxide directly target PML/RARA-mediated transcriptional repression and protein stability, inducing rapid differentiation of the promyelocytes and clinical remission in most APL patients. Arsenic Trioxide 28-44 PML nuclear body scaffold Homo sapiens 61-64 20378816-0 2010 Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 42-45 20378816-0 2010 Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 87-90 20378816-2 2010 Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 202-205 20378816-2 2010 Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). Arsenic Trioxide 18-23 PML nuclear body scaffold Homo sapiens 141-144 20378816-2 2010 Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). Arsenic Trioxide 18-23 PML nuclear body scaffold Homo sapiens 202-205 20378816-6 2010 The identification of PML as a direct target of As2O3 provides new insights into the drug"s mechanism of action and its specificity for APL. Arsenic Trioxide 48-53 PML nuclear body scaffold Homo sapiens 22-25 20098508-0 2009 Ascorbic Acid Potentiation of Arsenic Trioxide Anticancer Activity Against Acute Promyelocytic Leukemia. Arsenic Trioxide 30-46 PML nuclear body scaffold Homo sapiens 81-103 19815840-0 2010 Mobilization of PML/RARalpha negative peripheral blood stem cells with a combination of G-CSF and CXCR4 blockade in relapsed acute promyelocytic leukemia pre-treated with arsenic trioxide. Arsenic Trioxide 171-187 PML nuclear body scaffold Homo sapiens 16-19 19380586-3 2009 PML sumoylation and proteasome-dependent degradation induced by the E3 ubiquitin ligase, RNF4, are enhanced by the acute promyelocytic leukemia therapeutic agent, arsenic trioxide (As2O3). Arsenic Trioxide 163-179 PML nuclear body scaffold Homo sapiens 0-3 19702568-2 2009 All-trans retinoic acid (ATRA) and arsenic trioxide, which are the major molecularly targeted therapies in APL, affect or degrade the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. Arsenic Trioxide 35-51 PML nuclear body scaffold Homo sapiens 134-137 19380586-3 2009 PML sumoylation and proteasome-dependent degradation induced by the E3 ubiquitin ligase, RNF4, are enhanced by the acute promyelocytic leukemia therapeutic agent, arsenic trioxide (As2O3). Arsenic Trioxide 181-186 PML nuclear body scaffold Homo sapiens 0-3 19380586-6 2009 We found that, although dispensable for As2O3-enhanced PML sumoylation and RNF4 interaction, PML SBD core sequence was required for As2O3- and RNF4-induced PML degradation. Arsenic Trioxide 40-45 PML nuclear body scaffold Homo sapiens 55-58 19380586-6 2009 We found that, although dispensable for As2O3-enhanced PML sumoylation and RNF4 interaction, PML SBD core sequence was required for As2O3- and RNF4-induced PML degradation. Arsenic Trioxide 132-137 PML nuclear body scaffold Homo sapiens 93-96 19380586-6 2009 We found that, although dispensable for As2O3-enhanced PML sumoylation and RNF4 interaction, PML SBD core sequence was required for As2O3- and RNF4-induced PML degradation. Arsenic Trioxide 132-137 PML nuclear body scaffold Homo sapiens 93-96 19041605-3 2008 Arsenic trioxide (ATO) targets the PML moiety and has different mechanisms of action at different concentrations, and induces differentiation and apoptosis. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 35-38 19109388-4 2009 To clarify the mechanism of the anti-HCV activity of ATO, we examined whether or not PML is associated with this anti-HCV activity, since PML is known to be a target of ATO. Arsenic Trioxide 169-172 PML nuclear body scaffold Homo sapiens 138-141 19109388-5 2009 Interestingly, we observed the cytoplasmic translocation of PML after treatment with ATO. Arsenic Trioxide 85-88 PML nuclear body scaffold Homo sapiens 60-63 19273155-4 2009 The treatment of APL patients with all-transretinoic acid (ATRA) and arsenic trioxide which target the PML-RARA oncoprotein results in clinical remission, associated with blast cell differentiation and reformation of the PML NBs, thus linking NB integrity with disease status. Arsenic Trioxide 69-85 PML nuclear body scaffold Homo sapiens 103-106 19273155-4 2009 The treatment of APL patients with all-transretinoic acid (ATRA) and arsenic trioxide which target the PML-RARA oncoprotein results in clinical remission, associated with blast cell differentiation and reformation of the PML NBs, thus linking NB integrity with disease status. Arsenic Trioxide 69-85 PML nuclear body scaffold Homo sapiens 221-224 19041605-3 2008 Arsenic trioxide (ATO) targets the PML moiety and has different mechanisms of action at different concentrations, and induces differentiation and apoptosis. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 35-38 18636556-4 2008 By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. Arsenic Trioxide 336-339 PML nuclear body scaffold Homo sapiens 70-73 18636556-4 2008 By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. Arsenic Trioxide 151-154 PML nuclear body scaffold Homo sapiens 188-191 18636556-4 2008 By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. Arsenic Trioxide 151-154 PML nuclear body scaffold Homo sapiens 188-191 18636556-4 2008 By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. Arsenic Trioxide 336-339 PML nuclear body scaffold Homo sapiens 188-191 18636556-4 2008 By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. Arsenic Trioxide 336-339 PML nuclear body scaffold Homo sapiens 188-191 18636556-7 2008 PML/RARalpha that bestows NB4 cells various pathological features, paradoxically also endows these cells with the basis for susceptibility to ATO-induced cytotoxcity. Arsenic Trioxide 142-145 PML nuclear body scaffold Homo sapiens 0-3 26549974-0 2008 ASCORBIC ACID - MODULATION OF ARSENIC TRIOXIDE TOXICITY: IMPLICATION FOR THE CLINICAL TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA. Arsenic Trioxide 30-46 PML nuclear body scaffold Homo sapiens 105-127 18708055-2 2008 Here we show that arsenic trioxide (ATO) increases SUMO-2/3 modification of promyelocytic leukemia (PML) leading to its subsequent ubiquitylation in vivo. Arsenic Trioxide 18-34 PML nuclear body scaffold Homo sapiens 100-103 18708055-2 2008 Here we show that arsenic trioxide (ATO) increases SUMO-2/3 modification of promyelocytic leukemia (PML) leading to its subsequent ubiquitylation in vivo. Arsenic Trioxide 36-39 PML nuclear body scaffold Homo sapiens 100-103 18708055-3 2008 The SUMO-binding ubiquitin ligase RNF4 mediates this modification and causes disruption of PML nuclear bodies upon treatment with ATO. Arsenic Trioxide 130-133 PML nuclear body scaffold Homo sapiens 91-94 18708055-5 2008 Polysumoylation of PML in response to ATO thus leads to its recognition and ubiquitylation by RNF4. Arsenic Trioxide 38-41 PML nuclear body scaffold Homo sapiens 19-22 18408733-1 2008 In acute promyelocytic leukaemia (APL), arsenic trioxide induces degradation of the fusion protein encoded by the PML-RARA oncogene, differentiation of leukaemic cells and produces clinical remissions. Arsenic Trioxide 40-56 PML nuclear body scaffold Homo sapiens 114-117 18413806-7 2008 Importantly, arsenic trioxide treatment stimulated HMGA2 SUMOylation, leading to the formation of HMGA2 nuclear foci surrounding PML nuclear bodies and the stimulation of PML degradation. Arsenic Trioxide 13-29 PML nuclear body scaffold Homo sapiens 129-132 18413806-7 2008 Importantly, arsenic trioxide treatment stimulated HMGA2 SUMOylation, leading to the formation of HMGA2 nuclear foci surrounding PML nuclear bodies and the stimulation of PML degradation. Arsenic Trioxide 13-29 PML nuclear body scaffold Homo sapiens 171-174 18716620-6 2008 Remarkably, treatment with drugs that trigger PML-RARalpha degradation, such as all-trans retinoic acid or arsenic trioxide, restore nuclear PTEN. Arsenic Trioxide 107-123 PML nuclear body scaffold Homo sapiens 46-49 18708055-0 2008 Arsenic trioxide stimulates SUMO-2/3 modification leading to RNF4-dependent proteolytic targeting of PML. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 101-104 17706770-3 2008 We have evaluated effects of ATRA and As2O3 treatment in PML-RARalpha-negative HL60 promyelocytic leukemia cells, harboring amplified c-myc. Arsenic Trioxide 38-43 PML nuclear body scaffold Homo sapiens 57-60 14706140-1 2003 Detection of the PML/RARalpha fusion gene by RT-PCR in acute promyelocytic leukemia (APL) blasts is not only critical to commence promptly the specific therapy with all-trans retinoic acid (ATRA) or arsenic trioxide (As(2)O(3)), but also essential for the definition of PML breakpoint type and subsequent monitoring of minimal residual disease (MRD). Arsenic Trioxide 199-215 PML nuclear body scaffold Homo sapiens 17-20 17317642-16 2007 Strikingly, a clearance of PML-RARalpha transcript in an earlier and more thorough manner, and a higher quality remission and survival in newly diagnosed APL are achieved when ATRA is combined with ATO, as compared to either monotherapy, making APL a curable disease. Arsenic Trioxide 198-201 PML nuclear body scaffold Homo sapiens 27-30 17081986-6 2006 We further demonstrate that arsenic trioxide-induced sumoylation of PML correlates with a change of endogenous Daxx partitioning from GR-regulated gene promoter to PODs and a relief of Daxx repression on GR target gene expression. Arsenic Trioxide 28-44 PML nuclear body scaffold Homo sapiens 68-71 16891316-0 2006 ATR, PML, and CHK2 play a role in arsenic trioxide-induced apoptosis. Arsenic Trioxide 34-50 PML nuclear body scaffold Homo sapiens 5-8 16891316-1 2006 Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RARalpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RARalpha. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 182-185 16891316-1 2006 Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RARalpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RARalpha. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 240-243 16891316-1 2006 Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RARalpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RARalpha. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 182-185 16891316-1 2006 Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RARalpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RARalpha. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 240-243 16891316-9 2006 Based on this, we propose that a pathway composed of ATR, PML, Chk2, and p53 plays a role in ATO-mediated apoptosis, a notion that is consistent with the observation that Chk2 is genetically intact and mutations in the p53 gene are extremely rare in APL. Arsenic Trioxide 93-96 PML nuclear body scaffold Homo sapiens 58-61 16330433-2 2005 Here, we investigate whether these two agents influence the in vitro differentiation-inducing effect of arsenic trioxide (As2O3) on AML cells, an effective drug for the treatment of acute promyelocytic leukemia (APL) that is a unique subtype of AML with a specific fusion protein, PML-RARalpha. Arsenic Trioxide 104-120 PML nuclear body scaffold Homo sapiens 281-284 16330433-9 2005 These two hypoxia-mimetic agents also accelerated As2O3-induced modulation and degradation of PML-RARalpha protein in NB4 cells. Arsenic Trioxide 50-55 PML nuclear body scaffold Homo sapiens 94-97 16330433-11 2005 INTERPRETATION AND CONCLUSIONS: Mimicked hypoxia enhanced As2O3-induced differentiation, in which HIF-1alpha and PML/RARalpha proteins played an important role. Arsenic Trioxide 58-63 PML nuclear body scaffold Homo sapiens 113-116 15093545-0 2004 Phosphorylation of PML by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis. Arsenic Trioxide 80-96 PML nuclear body scaffold Homo sapiens 19-22 14668793-8 2003 As2O3 differently altered IFN-induced gene products; it downregulated PML/RARalpha and PML, did not alter PKR and Stat1, and upregulated interferon regulatory family (IRF)-1. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 70-73 14668793-8 2003 As2O3 differently altered IFN-induced gene products; it downregulated PML/RARalpha and PML, did not alter PKR and Stat1, and upregulated interferon regulatory family (IRF)-1. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 87-90 17929112-6 2007 Arsenic trioxide triggers the rapid degradation of PML-RARalpha through the targeting of the PML moieties of the fusion protein and showed a high CR rate in relapsed APL. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 51-54 17929112-6 2007 Arsenic trioxide triggers the rapid degradation of PML-RARalpha through the targeting of the PML moieties of the fusion protein and showed a high CR rate in relapsed APL. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 93-96 17202112-4 2007 We investigated the mechanism of arsenite-induced PML/RAR alpha degradation. Arsenic Trioxide 33-41 PML nuclear body scaffold Homo sapiens 50-63 17202112-14 2007 PML/RAR alpha was degraded by lysate from arsenite-treated APL cells, and the degradation was inhibited by protease inhibitors. Arsenic Trioxide 42-50 PML nuclear body scaffold Homo sapiens 0-13 17468032-2 2007 The ability of retinoic acid (RA) and arsenic trioxide to directly target the oncogenic promyelocytic leukemia-retinoic receptor A (PML-RARA) fusion protein also made this disease the first model for oncogene-targeted therapies. Arsenic Trioxide 38-54 PML nuclear body scaffold Homo sapiens 132-135 16804937-0 2006 Use of Novoseven for arsenic trioxide-induced bleeding in PML. Arsenic Trioxide 21-37 PML nuclear body scaffold Homo sapiens 58-61 16331271-11 2006 Similarly to what was observed in human APL patients, we found that NPM/RAR alpha and PML/RAR alpha, but not PLZF/RAR alpha leukemia, was responsive to all-trans retinoic acid (ATRA) or As2O3 treatments. Arsenic Trioxide 186-191 PML nuclear body scaffold Homo sapiens 86-99 15160934-4 2004 The mechanism of action of both ATRA and As2O3 appears to be by inducing granulocytic differentiation and this cellular differentiation seems to depend on PML-RARalpha proteolysis. Arsenic Trioxide 41-46 PML nuclear body scaffold Homo sapiens 155-158 15160934-6 2004 As2O3 treatment results in only complete degradation of PML-RARalpha protein in both ATRA-sensitive and -resistant APL cells. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 56-59 15160934-8 2004 Therefore, PML-RARalpha proteolysis induced by ATRA and As2O3 may play an important role in overcoming the repressive activity of PML-RARalpha and allowing cellular differentiation to proceed. Arsenic Trioxide 56-61 PML nuclear body scaffold Homo sapiens 11-14 15160934-8 2004 Therefore, PML-RARalpha proteolysis induced by ATRA and As2O3 may play an important role in overcoming the repressive activity of PML-RARalpha and allowing cellular differentiation to proceed. Arsenic Trioxide 56-61 PML nuclear body scaffold Homo sapiens 130-133 15461930-1 2004 The use of arsenic-containing compounds in cancer therapy is currently being re-considered, after the recent approval of arsenic trioxide (Trisenox) for the treatment of relapsed promyelocytic leukemia (PML). Arsenic Trioxide 121-137 PML nuclear body scaffold Homo sapiens 203-206 15461930-1 2004 The use of arsenic-containing compounds in cancer therapy is currently being re-considered, after the recent approval of arsenic trioxide (Trisenox) for the treatment of relapsed promyelocytic leukemia (PML). Arsenic Trioxide 139-147 PML nuclear body scaffold Homo sapiens 203-206 12915590-4 2003 Cellular stress and DNA damage caused by UV-radiation, downregulation of the proteasome and arsenic trioxide promoted Mdm2 and PML damage-specific nuclear relocalization and interaction in a p53-independent manner. Arsenic Trioxide 92-108 PML nuclear body scaffold Homo sapiens 127-130 14534537-3 2003 The response to As2O3 is genetically determined by the t(15;17)-or the t(9;22)-specific fusion proteins PML/RARalpha or BCR/ABL. Arsenic Trioxide 16-21 PML nuclear body scaffold Homo sapiens 104-107 14534537-4 2003 The PML portion of PML/RARalpha is crucial for the sensitivity to As2O3. Arsenic Trioxide 66-71 PML nuclear body scaffold Homo sapiens 4-7 14534537-4 2003 The PML portion of PML/RARalpha is crucial for the sensitivity to As2O3. Arsenic Trioxide 66-71 PML nuclear body scaffold Homo sapiens 19-22 14534537-9 2003 To disclose the mechanism of As2O3-induced apoptosis in PML/RARalpha- and BCR/ABL-expressing cells, we focused on the role of PML for As2O3-induced cell death. Arsenic Trioxide 29-34 PML nuclear body scaffold Homo sapiens 56-59 14534537-9 2003 To disclose the mechanism of As2O3-induced apoptosis in PML/RARalpha- and BCR/ABL-expressing cells, we focused on the role of PML for As2O3-induced cell death. Arsenic Trioxide 134-139 PML nuclear body scaffold Homo sapiens 126-129 12895391-2 2003 Reverse-transcription polymerase chain reaction (RT-PCR) amplification of PML-RARalpha messenger RNA can establish the diagnosis of APL, predict response to all-trans retinoic acid and arsenic trioxide, detect minimal residual disease, and predict relapse. Arsenic Trioxide 185-201 PML nuclear body scaffold Homo sapiens 74-77 12795834-1 2003 OBJECTIVE: To investigate the mechanism of arsenic trioxide (As(2)O(3)) induced apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix related protein promyelocytic leukaemia (PML). Arsenic Trioxide 43-59 PML nuclear body scaffold Homo sapiens 177-200 12795834-1 2003 OBJECTIVE: To investigate the mechanism of arsenic trioxide (As(2)O(3)) induced apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix related protein promyelocytic leukaemia (PML). Arsenic Trioxide 43-59 PML nuclear body scaffold Homo sapiens 202-205 12795834-1 2003 OBJECTIVE: To investigate the mechanism of arsenic trioxide (As(2)O(3)) induced apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix related protein promyelocytic leukaemia (PML). Arsenic Trioxide 61-70 PML nuclear body scaffold Homo sapiens 177-200 12795834-1 2003 OBJECTIVE: To investigate the mechanism of arsenic trioxide (As(2)O(3)) induced apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix related protein promyelocytic leukaemia (PML). Arsenic Trioxide 61-70 PML nuclear body scaffold Homo sapiens 202-205 12667397-0 2003 Nuclear matrix associated protein PML: an arsenic trioxide apoptosis therapeutic target protein in HepG2 cells. Arsenic Trioxide 42-58 PML nuclear body scaffold Homo sapiens 34-37 12429934-1 2002 Arsenic trioxide (As(2)O(3)) is highly effective in the treatment of acute promyelocytic leukemias that express the promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARalpha) fusion protein. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 169-172 11704843-5 2001 The effect of As(2)O(3) has been shown to be related to the expression of APL-specific PML-RARalpha oncoprotein, and there is a synergistic effect between As(2)O(3) and ATRA in an APL mouse model. Arsenic Trioxide 14-23 PML nuclear body scaffold Homo sapiens 87-90 11890109-7 2002 At both concentrations, As2O3 causes degradation of PML-RAR alpha protein implicated probably in its mechanisms of action. Arsenic Trioxide 24-29 PML nuclear body scaffold Homo sapiens 52-55 11704854-0 2001 Pathways of retinoic acid- or arsenic trioxide-induced PML/RARalpha catabolism, role of oncogene degradation in disease remission. Arsenic Trioxide 30-46 PML nuclear body scaffold Homo sapiens 55-58 11413191-0 2001 Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. Arsenic Trioxide 107-112 PML nuclear body scaffold Homo sapiens 8-30 11413191-0 2001 Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. Arsenic Trioxide 107-112 PML nuclear body scaffold Homo sapiens 121-124 11413191-3 2001 PML is conjugated by the ubiquitin-related peptide SUMO-1, a process enhanced by As2O3 and proposed to target PML to the nuclear matrix. Arsenic Trioxide 81-86 PML nuclear body scaffold Homo sapiens 0-3 11413191-3 2001 PML is conjugated by the ubiquitin-related peptide SUMO-1, a process enhanced by As2O3 and proposed to target PML to the nuclear matrix. Arsenic Trioxide 81-86 PML nuclear body scaffold Homo sapiens 110-113 11413191-4 2001 We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARalpha and that this process requires a specific sumolation site in PML, K160. Arsenic Trioxide 20-25 PML nuclear body scaffold Homo sapiens 75-78 11413191-4 2001 We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARalpha and that this process requires a specific sumolation site in PML, K160. Arsenic Trioxide 20-25 PML nuclear body scaffold Homo sapiens 83-86 11413191-4 2001 We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARalpha and that this process requires a specific sumolation site in PML, K160. Arsenic Trioxide 20-25 PML nuclear body scaffold Homo sapiens 83-86 11413191-8 2001 Therefore, studying the basis of As2O3-induced PML/RARalpha degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation. Arsenic Trioxide 33-38 PML nuclear body scaffold Homo sapiens 47-50 11413191-8 2001 Therefore, studying the basis of As2O3-induced PML/RARalpha degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation. Arsenic Trioxide 33-38 PML nuclear body scaffold Homo sapiens 85-88 11413191-0 2001 Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. Arsenic Trioxide 107-112 PML nuclear body scaffold Homo sapiens 121-124 11133770-1 2001 All-trans retinoic acid (tRA) and arsenic trioxide (As(2)O(3)) induce non-cross-resistant complete clinical remission in patients with acute promyelocytic leukemia with t(15;17) translocation and target PML-RARalpha, the leukemogenic protein, by different pathways suggesting a possible therapeutic synergism. Arsenic Trioxide 34-50 PML nuclear body scaffold Homo sapiens 203-206 11133770-1 2001 All-trans retinoic acid (tRA) and arsenic trioxide (As(2)O(3)) induce non-cross-resistant complete clinical remission in patients with acute promyelocytic leukemia with t(15;17) translocation and target PML-RARalpha, the leukemogenic protein, by different pathways suggesting a possible therapeutic synergism. Arsenic Trioxide 52-61 PML nuclear body scaffold Homo sapiens 203-206 11172537-4 2001 As2O3 over a wide range of concentrations (0.1 to 2.0 micromol/L) Induces degradation of PML-RARalpha as well as the wild-type PML and enhances the acetylation of histone, a process important for the transcriptional activation of genes. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 89-92 11779431-7 2001 Both ATRA and As2O3 can also down-regulate the TF antigen in U937 cells transfected with or without PML-RARa. Arsenic Trioxide 14-19 PML nuclear body scaffold Homo sapiens 100-103 11172537-4 2001 As2O3 over a wide range of concentrations (0.1 to 2.0 micromol/L) Induces degradation of PML-RARalpha as well as the wild-type PML and enhances the acetylation of histone, a process important for the transcriptional activation of genes. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 127-130 11172537-9 2001 The in vivo effect of As2O3 seems to be related to the expression of APL-specific PML-RARalpha oncoprotein, and a synergistic effect between As2O3 and ATRA has been shown in the APL mouse model. Arsenic Trioxide 22-27 PML nuclear body scaffold Homo sapiens 82-85 11721366-5 1999 As2O3 had no effect on the expression of the apoptosis-related genes like Bcl-2, Bcl-xL/S, Bax, ICH-1L, p53, PARP, either, but downregulated PML protein expression in K562 cells. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 141-144 10910048-2 2000 In acute promyelocytic leukemia response to arsenic trioxide (As2O3) has been shown to be genetically determined by the acute promyelocytic leukemia-specific t(15;17) translocation product PML/RARalpha. Arsenic Trioxide 44-60 PML nuclear body scaffold Homo sapiens 189-192 10910048-2 2000 In acute promyelocytic leukemia response to arsenic trioxide (As2O3) has been shown to be genetically determined by the acute promyelocytic leukemia-specific t(15;17) translocation product PML/RARalpha. Arsenic Trioxide 62-67 PML nuclear body scaffold Homo sapiens 189-192 10830735-6 2000 As2O3 can induce partial differentiation and subsequent apoptosis of APL cells through degradation of wild type PML and PML/RAR alpha chimeric proteins and possible anti-mitochondrial effects. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 112-115 10830735-8 2000 Nevertheless, the PML/RAR alpha fusion protein was reported to disappear in some APL patients who received As2O3, and who might earn long-survival. Arsenic Trioxide 107-112 PML nuclear body scaffold Homo sapiens 18-31 11798775-1 2000 OBJECTIVE: To illustrate the possible roles of acute promyelocytic leukemia-specific chimeric proteins PML-RARalpha and PLZF-RARalpha in the effects of arsenic trioxide (As(2)O(3)). Arsenic Trioxide 152-168 PML nuclear body scaffold Homo sapiens 103-106 11798775-10 2000 CONCLUSION: PML-RARalpha and PLZF-RARalpha markedly enhance growth-inhibitory effects of As2)O3) on K562 cells. Arsenic Trioxide 89-95 PML nuclear body scaffold Homo sapiens 12-15 10373566-3 1999 Recently it has been shown that complete remission can be achieved upon treatment with arsenic trioxide (As2O3) in PML-RARalpha-positive APL, even when the patient has relapsed and the disease is RA resistant. Arsenic Trioxide 87-103 PML nuclear body scaffold Homo sapiens 115-118 10373566-0 1999 PIC-1/SUMO-1-modified PML-retinoic acid receptor alpha mediates arsenic trioxide-induced apoptosis in acute promyelocytic leukemia. Arsenic Trioxide 64-80 PML nuclear body scaffold Homo sapiens 22-25 10373566-3 1999 Recently it has been shown that complete remission can be achieved upon treatment with arsenic trioxide (As2O3) in PML-RARalpha-positive APL, even when the patient has relapsed and the disease is RA resistant. Arsenic Trioxide 105-110 PML nuclear body scaffold Homo sapiens 115-118 9834237-5 1998 Intriguingly, As2O3 was also shown to induce degradation of the PML-RAR chimera and to reorganize PML nuclear bodies. Arsenic Trioxide 14-19 PML nuclear body scaffold Homo sapiens 64-67 10023688-5 1999 Arsenic trioxide, known to induce aggregation of PML nuclear bodies, left the microspeckled PLZF/RARalpha localization completely unaffected. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 49-52 10328107-12 1999 As2O3 induced PML (promyelocytic leukemia) protein degradation but did not modulate expression of cell cycle-related proteins, including c-myc, retinoblastoma protein, cyclin-dependent kinase 4, cyclin D1, and p53, or expression of differentiation-related antigens. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 14-17 10328107-12 1999 As2O3 induced PML (promyelocytic leukemia) protein degradation but did not modulate expression of cell cycle-related proteins, including c-myc, retinoblastoma protein, cyclin-dependent kinase 4, cyclin D1, and p53, or expression of differentiation-related antigens. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 19-41 9834237-9 1998 The mechanism of antimony action is likely to be similar to that of As2O3, notably both substances induce the attachment of the ubiquitin-like SUMO-1 molecule to the PML moiety of PML-RAR. Arsenic Trioxide 68-73 PML nuclear body scaffold Homo sapiens 166-169 9596679-1 1998 In the acute promyelocytic leukemia (APL) cell line NB4, as well as in APL patients" cells, arsenic trioxide (As2O3) leads to incomplete cell maturation, induction of apoptosis, as well as to the degradation of the oncogenic PML/RARalpha fusion protein. Arsenic Trioxide 92-108 PML nuclear body scaffold Homo sapiens 225-228 9716575-0 1998 Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML-RARalpha independent manner. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 111-114 9716575-0 1998 Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML-RARalpha independent manner. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 119-122 9716575-2 1998 As2O3 has been proposed to principally target PML and PML-RARalpha proteins in APL cells. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 46-49 9716575-2 1998 As2O3 has been proposed to principally target PML and PML-RARalpha proteins in APL cells. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 54-57 9716575-7 1998 As2O3 relocalized PML and PML-RARalpha onto nuclear bodies, which was followed by PML degradation in NB4 as well as in HL60 and U937 cell lines. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 18-21 9716575-7 1998 As2O3 relocalized PML and PML-RARalpha onto nuclear bodies, which was followed by PML degradation in NB4 as well as in HL60 and U937 cell lines. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 26-29 9716575-7 1998 As2O3 relocalized PML and PML-RARalpha onto nuclear bodies, which was followed by PML degradation in NB4 as well as in HL60 and U937 cell lines. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 26-29 9716575-9 1998 Moreover, both As2O3 and melarsoprol comparably inhibited growth and induced apoptosis of PML+/+ and PML-/- MEFs, and inhibited colony-forming unit erythroid (CFU-E) and CFU granulocyte-monocyte formation in BM cultures of PML+/+ and PML-/- progenitors. Arsenic Trioxide 15-20 PML nuclear body scaffold Homo sapiens 90-93 9716575-9 1998 Moreover, both As2O3 and melarsoprol comparably inhibited growth and induced apoptosis of PML+/+ and PML-/- MEFs, and inhibited colony-forming unit erythroid (CFU-E) and CFU granulocyte-monocyte formation in BM cultures of PML+/+ and PML-/- progenitors. Arsenic Trioxide 15-20 PML nuclear body scaffold Homo sapiens 101-104 9716575-9 1998 Moreover, both As2O3 and melarsoprol comparably inhibited growth and induced apoptosis of PML+/+ and PML-/- MEFs, and inhibited colony-forming unit erythroid (CFU-E) and CFU granulocyte-monocyte formation in BM cultures of PML+/+ and PML-/- progenitors. Arsenic Trioxide 15-20 PML nuclear body scaffold Homo sapiens 101-104 9716575-9 1998 Moreover, both As2O3 and melarsoprol comparably inhibited growth and induced apoptosis of PML+/+ and PML-/- MEFs, and inhibited colony-forming unit erythroid (CFU-E) and CFU granulocyte-monocyte formation in BM cultures of PML+/+ and PML-/- progenitors. Arsenic Trioxide 15-20 PML nuclear body scaffold Homo sapiens 101-104 9596679-1 1998 In the acute promyelocytic leukemia (APL) cell line NB4, as well as in APL patients" cells, arsenic trioxide (As2O3) leads to incomplete cell maturation, induction of apoptosis, as well as to the degradation of the oncogenic PML/RARalpha fusion protein. Arsenic Trioxide 110-115 PML nuclear body scaffold Homo sapiens 225-228 9596679-3 1998 When grown in the presence of As2O3, NB4-AsR cells degrade PML/RARalpha, slightly differentiate, and become more sensitive to serum deprivation-induced apoptosis. Arsenic Trioxide 30-35 PML nuclear body scaffold Homo sapiens 59-62 9596679-5 1998 Thus, As2O3- or retinoic acid (RA)-induced PML/RARalpha degradation may be a prerequisite, but is not sufficient for the full differentiative/apoptotic response to these drugs. Arsenic Trioxide 6-11 PML nuclear body scaffold Homo sapiens 43-46 9772451-7 1997 In addition, 0.1-2 mumol/L of As2O3 could rapidly and effectively modulate and degradate PML/PML-RAR alpha proteins. Arsenic Trioxide 30-35 PML nuclear body scaffold Homo sapiens 89-92 9450572-0 1998 Arsenic trioxide as an inducer of apoptosis and loss of PML/RAR alpha protein in acute promyelocytic leukemia cells. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 56-69 9427741-4 1998 Here we show that, in APL cells, As2O3 triggers rapid degradation of PML-RARalpha and provokes the restoration of intact nuclear bodies. Arsenic Trioxide 33-38 PML nuclear body scaffold Homo sapiens 69-72 9427741-7 1998 As2O3 administration strikingly increases the pool of SUMO-1-PML conjugates that, subsequently, accumulate in enlarged nuclear bodies. Arsenic Trioxide 0-5 PML nuclear body scaffold Homo sapiens 61-64 9535176-8 1997 Modulation and degradation of PML-RAR alpha proteins can be induced by As2O3 and probably contribute to these two effects. Arsenic Trioxide 71-76 PML nuclear body scaffold Homo sapiens 30-33 9535176-9 1997 These studies lead to a model in which PML-RAR alpha could be the target of both ATRA differentiation therapy and As2O3 apoptosis therapy. Arsenic Trioxide 114-119 PML nuclear body scaffold Homo sapiens 39-42 9772451-7 1997 In addition, 0.1-2 mumol/L of As2O3 could rapidly and effectively modulate and degradate PML/PML-RAR alpha proteins. Arsenic Trioxide 30-35 PML nuclear body scaffold Homo sapiens 93-96 9772451-8 1997 CONCLUSION: As2O3 had double effects (induction of apoptosis and imcomplete differentiation) on NB4 cells, which could associate with rapid modulation and degradation of PML/PML-RAR alpha proteins. Arsenic Trioxide 12-17 PML nuclear body scaffold Homo sapiens 170-173 9772451-8 1997 CONCLUSION: As2O3 had double effects (induction of apoptosis and imcomplete differentiation) on NB4 cells, which could associate with rapid modulation and degradation of PML/PML-RAR alpha proteins. Arsenic Trioxide 12-17 PML nuclear body scaffold Homo sapiens 174-177 9129042-0 1997 Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Arsenic Trioxide 7-23 PML nuclear body scaffold Homo sapiens 58-90 9129042-0 1997 Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Arsenic Trioxide 25-30 PML nuclear body scaffold Homo sapiens 58-90 9129042-2 1997 The therapeutic effect of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) was evaluated among 15 APL patients at relapse after all-trans retinoic acid (ATRA) induced and chemotherapy maintained complete remission (CR). Arsenic Trioxide 26-42 PML nuclear body scaffold Homo sapiens 77-100 9129042-2 1997 The therapeutic effect of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) was evaluated among 15 APL patients at relapse after all-trans retinoic acid (ATRA) induced and chemotherapy maintained complete remission (CR). Arsenic Trioxide 44-49 PML nuclear body scaffold Homo sapiens 77-100 15622748-0 1997 [Effects of arsenic trioxide on the subcellular localization of PML/PML-RARalpha protein in leukemic cells]. Arsenic Trioxide 12-28 PML nuclear body scaffold Homo sapiens 64-67 15622748-2 1997 METHODS: Effects of As2O3 on the subcellular localization of PML-RARalpha in NB4 cells were studied. Arsenic Trioxide 20-25 PML nuclear body scaffold Homo sapiens 61-64 15622748-4 1997 CONCLUSION: As2O3-induced apoptosis was independent of the retinoic acid signal pathway, and it might be regulated by PML/PML-RARalpha and/or other related genes. Arsenic Trioxide 12-17 PML nuclear body scaffold Homo sapiens 118-121 15622748-4 1997 CONCLUSION: As2O3-induced apoptosis was independent of the retinoic acid signal pathway, and it might be regulated by PML/PML-RARalpha and/or other related genes. Arsenic Trioxide 12-17 PML nuclear body scaffold Homo sapiens 122-125 8986606-8 1996 We show that in APL, As2O3 leads to the rapid reformation of PML bodies. Arsenic Trioxide 21-26 PML nuclear body scaffold Homo sapiens 61-64 15622748-0 1997 [Effects of arsenic trioxide on the subcellular localization of PML/PML-RARalpha protein in leukemic cells]. Arsenic Trioxide 12-28 PML nuclear body scaffold Homo sapiens 68-71 15622748-1 1997 OBJECTIVE: In order to illustrate the possible roles of PML-RARalpha protein in arsenic trioxide (AsO3)-induced NB4 cell apoptosis. Arsenic Trioxide 80-96 PML nuclear body scaffold Homo sapiens 56-59 8704214-0 1996 In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Arsenic Trioxide 57-73 PML nuclear body scaffold Homo sapiens 223-226 8704214-0 1996 In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Arsenic Trioxide 57-73 PML nuclear body scaffold Homo sapiens 237-240 8704214-0 1996 In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Arsenic Trioxide 75-80 PML nuclear body scaffold Homo sapiens 223-226 8704214-0 1996 In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Arsenic Trioxide 75-80 PML nuclear body scaffold Homo sapiens 237-240 8704214-0 1996 In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Arsenic Trioxide 132-137 PML nuclear body scaffold Homo sapiens 223-226 8704214-0 1996 In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Arsenic Trioxide 132-137 PML nuclear body scaffold Homo sapiens 237-240 8704214-6 1996 (3) As2O3 induces a significant modulation of the PML staining pattern in NB4 cells and HL-60 cells. Arsenic Trioxide 4-9 PML nuclear body scaffold Homo sapiens 50-53 8704214-7 1996 The micropunctates characteristic of PML-RAR alpha in NB4 cells dissappear after treatment with As2O3, whereas a diffuse PML staining occurs in the perinuclear cytoplasmic region. Arsenic Trioxide 96-101 PML nuclear body scaffold Homo sapiens 37-40 34310740-1 2021 Under the differentiation induction therapy with all-trans retinoic acid and arsenic trioxide, nearly 95% of typical acute promyelocyte leukemia (APL), which is characterized by the presence of PML-RARA, patients can be cured. Arsenic Trioxide 77-93 PML nuclear body scaffold Homo sapiens 194-197 15894607-0 2005 Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Arsenic Trioxide 64-80 PML nuclear body scaffold Homo sapiens 123-145 35622143-1 2022 Acute promyelocytic leukemia (APL) is a hematological malignancy driven by the oncoprotein PML-RARalpha, which can be treated with arsenic trioxide (As2O3) or/and all-trans retinoic acid. Arsenic Trioxide 131-147 PML nuclear body scaffold Homo sapiens 91-94 35622143-1 2022 Acute promyelocytic leukemia (APL) is a hematological malignancy driven by the oncoprotein PML-RARalpha, which can be treated with arsenic trioxide (As2O3) or/and all-trans retinoic acid. Arsenic Trioxide 149-154 PML nuclear body scaffold Homo sapiens 91-94 35622143-7 2022 Notably, As2O3 treatment triggers the dissociation of PRMT5 from PML nuclear bodies, attenuating RNF4 methylation and promoting RNF4-mediated PML-RARalpha ubiquitination and degradation. Arsenic Trioxide 9-14 PML nuclear body scaffold Homo sapiens 65-68 32854112-5 2021 All-trans retinoic acid and arsenic trioxide, two widely used drugs in APL therapy, exert synergistic effects on controlling super-enhancer-associated PML/RARalpha-regulated targets in APL cells. Arsenic Trioxide 28-44 PML nuclear body scaffold Homo sapiens 151-154 32435915-2 2020 In contrast, arsenic trioxide (As2O3) is an effective therapeutic agent for the treatment of acute promyelocytic leukemia, in which the binding of arsenite (iAsIII) to promyelocytic leukemia (PML) protein is the proposed initial step. Arsenic Trioxide 13-29 PML nuclear body scaffold Homo sapiens 192-195 32882258-3 2020 Arsenic trioxide (ATO) is one of the most common drugs used in the frontline treatment of APL that act through targeting and destabilizing the PML/RARalpha oncofusion protein. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 143-146 32882258-3 2020 Arsenic trioxide (ATO) is one of the most common drugs used in the frontline treatment of APL that act through targeting and destabilizing the PML/RARalpha oncofusion protein. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 143-146 33091440-3 2020 Mechanistically, ATO can induce PML/RARalpha fusion protein degradation, causing APL cell differentiation and apoptosis. Arsenic Trioxide 17-20 PML nuclear body scaffold Homo sapiens 32-35 32435915-2 2020 In contrast, arsenic trioxide (As2O3) is an effective therapeutic agent for the treatment of acute promyelocytic leukemia, in which the binding of arsenite (iAsIII) to promyelocytic leukemia (PML) protein is the proposed initial step. Arsenic Trioxide 31-36 PML nuclear body scaffold Homo sapiens 192-195 31670356-0 2019 Irreversibility of arsenic trioxide induced PML/RARalpha fusion protein solubility changes. Arsenic Trioxide 19-35 PML nuclear body scaffold Homo sapiens 44-56 32223133-1 2020 Arsenic trioxide (ATO) is a therapeutic agents used to treat acute promyelocytic leukemia (APL), a disease caused by a chromosomal translocation of the retinoic acid receptor a (RARalpha) gene that can occur reciprocally with the promyelocytic leukemia (PML) gene. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 67-89 32223133-1 2020 Arsenic trioxide (ATO) is a therapeutic agents used to treat acute promyelocytic leukemia (APL), a disease caused by a chromosomal translocation of the retinoic acid receptor a (RARalpha) gene that can occur reciprocally with the promyelocytic leukemia (PML) gene. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 254-257 32223133-1 2020 Arsenic trioxide (ATO) is a therapeutic agents used to treat acute promyelocytic leukemia (APL), a disease caused by a chromosomal translocation of the retinoic acid receptor a (RARalpha) gene that can occur reciprocally with the promyelocytic leukemia (PML) gene. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 67-89 32223133-1 2020 Arsenic trioxide (ATO) is a therapeutic agents used to treat acute promyelocytic leukemia (APL), a disease caused by a chromosomal translocation of the retinoic acid receptor a (RARalpha) gene that can occur reciprocally with the promyelocytic leukemia (PML) gene. Arsenic Trioxide 18-21 PML nuclear body scaffold Homo sapiens 254-257 32223133-4 2020 Our analyses revealed that low dose of ATO resulted in the differential modification of selected substrates including the SUMOylation (K380, K394, K490 and K497) and ubiquitylation (K337, K401) of PML. Arsenic Trioxide 39-42 PML nuclear body scaffold Homo sapiens 197-200 32328411-8 2020 ATO treatment blocks virus expression and replication by reducing the number and integrity of promyelocytic leukemia (PML) nuclear bodies, important subnuclear structures for HAdV replication. Arsenic Trioxide 0-3 PML nuclear body scaffold Homo sapiens 118-121 32328411-10 2020 ATO reduces levels of viral SUMO-E2A protein, while increasing SUMO-PML, suggesting that ATO interferes with SUMOylation of proteins crucial for HAdV replication. Arsenic Trioxide 0-3 PML nuclear body scaffold Homo sapiens 68-71 31670356-1 2019 Arsenic trioxide (As2O3) is one of the most effective drugs for the treatment of acute promyelocytic leukemia (APL), and induces the degradation of chimeric oncoprotein PML/RARalpha (P/R) and APL cell differentiation. Arsenic Trioxide 18-23 PML nuclear body scaffold Homo sapiens 169-172 32240679-0 2020 Role of PML SUMOylation in arsenic trioxide-induced fibrosis in HSCs. Arsenic Trioxide 27-43 PML nuclear body scaffold Homo sapiens 8-11 32240679-1 2020 BACKGROUND: Arsenic trioxide (ATO) can bind directly to the human promyelocytic leukemia (PML) protein, leading to modification of PML by SUMOs. Arsenic Trioxide 12-28 PML nuclear body scaffold Homo sapiens 66-102 32240679-1 2020 BACKGROUND: Arsenic trioxide (ATO) can bind directly to the human promyelocytic leukemia (PML) protein, leading to modification of PML by SUMOs. Arsenic Trioxide 12-28 PML nuclear body scaffold Homo sapiens 90-93 32240679-1 2020 BACKGROUND: Arsenic trioxide (ATO) can bind directly to the human promyelocytic leukemia (PML) protein, leading to modification of PML by SUMOs. Arsenic Trioxide 30-33 PML nuclear body scaffold Homo sapiens 66-102 32240679-1 2020 BACKGROUND: Arsenic trioxide (ATO) can bind directly to the human promyelocytic leukemia (PML) protein, leading to modification of PML by SUMOs. Arsenic Trioxide 30-33 PML nuclear body scaffold Homo sapiens 90-93 32240679-7 2020 OBJECTIVE: This study aimed to investigate the role of PML Sumoylation in the ATO-induced HSCs activation and to improve the mechanism of ATO-induced liver fibrosis. Arsenic Trioxide 78-81 PML nuclear body scaffold Homo sapiens 55-58 32163072-4 2020 Here, we introduce in depth the latest evidence and detailed insights into ATO-mediated cures for APL by targeting PML/RARalpha chimeric protein, followed by the preclinical and clinical efficacy of ATO on various non-APL malignancies and solid tumors. Arsenic Trioxide 75-78 PML nuclear body scaffold Homo sapiens 115-118 31670356-1 2019 Arsenic trioxide (As2O3) is one of the most effective drugs for the treatment of acute promyelocytic leukemia (APL), and induces the degradation of chimeric oncoprotein PML/RARalpha (P/R) and APL cell differentiation. Arsenic Trioxide 0-16 PML nuclear body scaffold Homo sapiens 169-172