PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 19815544-4 2009 Insig-1 is rapidly degraded by proteasomes when cells are depleted of cholesterol, and its degradation is inhibited when sterols accumulate in cells. Sterols 121-128 insulin induced gene 1 Homo sapiens 0-7 20482385-4 2010 This degradation results from the accumulation of sterols in ER membranes, which triggers binding of reductase to ER membrane proteins called Insig-1 and Insig-2. Sterols 50-57 insulin induced gene 1 Homo sapiens 142-149 19458199-10 2009 Coimmunoprecipitation experiments demonstrate sterol-stimulated association between HMG(350)-HA and Insig-1-Myc. Sterols 46-52 insulin induced gene 1 Homo sapiens 100-107 19638338-2 2009 This degradation results from sterol-induced binding of the membrane domain of reductase to endoplasmic reticulum membrane proteins called Insig-1 and Insig-2, which are carriers of a ubiquitin ligase called gp78. Sterols 30-36 insulin induced gene 1 Homo sapiens 139-146 18835813-2 2008 We showed previously that sterols inhibit this degradation by blocking ubiquitination of Insig-1. Sterols 26-33 insulin induced gene 1 Homo sapiens 89-96 18835813-7 2008 Unsaturated fatty acid-mediated stabilization of Insig-1 enhances the ability of sterols to inhibit proteolytic activation of SREBP-1, which activates transcription of genes involved in fatty acid synthesis. Sterols 81-88 insulin induced gene 1 Homo sapiens 49-56 17043353-5 2006 Sterols prevent Insig-1 ubiquitination and degradation by displacing gp78 from Insig-1, an event that results from sterol-induced binding of Scap to Insig-1. Sterols 115-121 insulin induced gene 1 Homo sapiens 16-23 17043353-5 2006 Sterols prevent Insig-1 ubiquitination and degradation by displacing gp78 from Insig-1, an event that results from sterol-induced binding of Scap to Insig-1. Sterols 115-121 insulin induced gene 1 Homo sapiens 79-86 17043353-5 2006 Sterols prevent Insig-1 ubiquitination and degradation by displacing gp78 from Insig-1, an event that results from sterol-induced binding of Scap to Insig-1. Sterols 115-121 insulin induced gene 1 Homo sapiens 79-86 17043353-6 2006 In addition to providing a mechanism for sterol-regulated degradation of Insig-1, these results help to explain why Scap is subject to endoplasmic reticulum retention upon Insig-1 binding, whereas 3-hydroxy-3-methylglutaryl coenzyme A reductase is ubiquitinated and degraded. Sterols 41-47 insulin induced gene 1 Homo sapiens 73-80 17043353-6 2006 In addition to providing a mechanism for sterol-regulated degradation of Insig-1, these results help to explain why Scap is subject to endoplasmic reticulum retention upon Insig-1 binding, whereas 3-hydroxy-3-methylglutaryl coenzyme A reductase is ubiquitinated and degraded. Sterols 41-47 insulin induced gene 1 Homo sapiens 172-179 18504457-4 2008 Accumulation of certain sterols triggers binding of reductase to endoplasmic reticulum (ER) membrane proteins called Insig-1 and Insig-2. Sterols 24-31 insulin induced gene 1 Homo sapiens 117-124 17043353-1 2006 Insig-1 and Insig-2, closely related endoplasmic reticulum membrane proteins, mediate transcriptional and post-transcriptional mechanisms that assure cholesterol homeostasis through their sterol-induced binding to Scap (SREBP cleavage-activating protein) and 3-hydroxy-3-methylglutaryl coenzyme A reductase. Sterols 155-161 insulin induced gene 1 Homo sapiens 0-7 17043353-2 2006 Recent studies show that Insig-1 (but not Insig-2) is ubiquitinated and rapidly degraded when cells are depleted of sterols. Sterols 116-123 insulin induced gene 1 Homo sapiens 25-32 17043353-3 2006 Conversely, ubiquitination of Insig-1 is blocked, and the protein is stabilized when intracellular sterols accumulate. Sterols 99-106 insulin induced gene 1 Homo sapiens 30-37 17043353-4 2006 Here, we report that the ubiquitin ligase gp78, which binds with much higher affinity to Insig-1 than Insig-2, is required for ubiquitination and degradation of Insig-1 in sterol-depleted cells. Sterols 172-178 insulin induced gene 1 Homo sapiens 89-96 17043353-4 2006 Here, we report that the ubiquitin ligase gp78, which binds with much higher affinity to Insig-1 than Insig-2, is required for ubiquitination and degradation of Insig-1 in sterol-depleted cells. Sterols 172-178 insulin induced gene 1 Homo sapiens 161-168 17043353-5 2006 Sterols prevent Insig-1 ubiquitination and degradation by displacing gp78 from Insig-1, an event that results from sterol-induced binding of Scap to Insig-1. Sterols 0-7 insulin induced gene 1 Homo sapiens 16-23 17043353-5 2006 Sterols prevent Insig-1 ubiquitination and degradation by displacing gp78 from Insig-1, an event that results from sterol-induced binding of Scap to Insig-1. Sterols 0-7 insulin induced gene 1 Homo sapiens 79-86 17043353-5 2006 Sterols prevent Insig-1 ubiquitination and degradation by displacing gp78 from Insig-1, an event that results from sterol-induced binding of Scap to Insig-1. Sterols 0-7 insulin induced gene 1 Homo sapiens 79-86 14563840-3 2003 Here, we use RNA interference to show that sterol-accelerated ubiquitination of reductase requires Insig-1 and Insig-2, membrane-bound proteins of the endoplasmic reticulum that were shown previously to accelerate degradation of reductase when overexpressed by transfection. Sterols 43-49 insulin induced gene 1 Homo sapiens 99-106 16606821-1 2006 Insig-1 and Insig-2 are closely related proteins of the endoplasmic reticulum (ER) that mediate feedback control of cholesterol synthesis by sterol-dependent binding to the following two membrane proteins: the escort protein Scap, thus preventing proteolytic processing of sterol regulatory element-binding proteins; and the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl CoA reductase, thus inducing the ubiquitination and ER-associated degradation of the enzyme. Sterols 121-127 insulin induced gene 1 Homo sapiens 0-7 16606821-1 2006 Insig-1 and Insig-2 are closely related proteins of the endoplasmic reticulum (ER) that mediate feedback control of cholesterol synthesis by sterol-dependent binding to the following two membrane proteins: the escort protein Scap, thus preventing proteolytic processing of sterol regulatory element-binding proteins; and the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl CoA reductase, thus inducing the ubiquitination and ER-associated degradation of the enzyme. Sterols 141-147 insulin induced gene 1 Homo sapiens 0-7 16606821-4 2006 The mutant Insig-1 was ineffective also in accelerating sterol-stimulated degradation of 3-hydroxy-3-methylglutaryl CoA reductase. Sterols 56-62 insulin induced gene 1 Homo sapiens 11-18 16549805-2 2006 In sterol-depleted cells Insig-1 is degraded at least 15 times more rapidly than Insig-2, owing to ubiquitination of Lys-156 and Lys-158 in Insig-1. Sterols 3-9 insulin induced gene 1 Homo sapiens 25-32 16549805-2 2006 In sterol-depleted cells Insig-1 is degraded at least 15 times more rapidly than Insig-2, owing to ubiquitination of Lys-156 and Lys-158 in Insig-1. Sterols 3-9 insulin induced gene 1 Homo sapiens 140-147 16399501-3 2006 In sterol-overloaded cells, Scap/SREBP binds to Insig-1, which retains the complex in the ER. Sterols 3-9 insulin induced gene 1 Homo sapiens 48-55 16399501-4 2006 Upon sterol deprivation, the Scap/SREBP complex dissociates from Insig-1, which is then ubiquitinated on lysines 156 and 158 and degraded in proteasomes. Sterols 5-11 insulin induced gene 1 Homo sapiens 65-72 14660594-3 2004 Under conditions of sterol excess, Insig-1 also binds to the ER enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, facilitating its ubiquitination and proteasomal degradation. Sterols 20-26 insulin induced gene 1 Homo sapiens 35-42 14660594-7 2004 The membranous nature of Insig-1 is consistent with its sterol-dependent binding to hydrophobic sterol-sensing domains in SCAP and HMG CoA reductase. Sterols 56-62 insulin induced gene 1 Homo sapiens 25-32 14660594-7 2004 The membranous nature of Insig-1 is consistent with its sterol-dependent binding to hydrophobic sterol-sensing domains in SCAP and HMG CoA reductase. Sterols 96-102 insulin induced gene 1 Homo sapiens 25-32 15899885-5 2005 This in vitro inhibition is dependent on the presence of Insig-1, an ER resident protein that is necessary for sterol-mediated inhibition of Scap/SREBP transport in intact cells. Sterols 111-117 insulin induced gene 1 Homo sapiens 57-64 15304479-3 2004 Here we report that hypotonic stress reverses the sterol-mediated inhibition of SREBP proteolytic activation by reducing the level of Insig-1 but not Insig-2. Sterols 50-56 insulin induced gene 1 Homo sapiens 134-141 12535518-3 2003 Here, we show that degradation of HMG CoA reductase is accelerated by the sterol-induced binding of its sterol-sensing domain to the ER protein insig-1. Sterols 74-80 insulin induced gene 1 Homo sapiens 144-151 12963821-3 2003 More recently, Insig-1 and Insig-2 were identified as ER resident proteins that bind the SCAP/SREBP complex and promote its ER retention when cells are treated with sterols. Sterols 165-172 insulin induced gene 1 Homo sapiens 15-22 12842885-3 2003 In sterol-treated cells, the SCAP/SREBP complex binds to Insig-1 or Insig-2, which retains the complex in the ER, blocking SREBP processing and decreasing lipid synthesis. Sterols 3-9 insulin induced gene 1 Homo sapiens 57-64 14587295-11 2003 Recent work has additionally uncovered integral membrane proteins, insig-1 and insig-2, that are required to retain the SREBP-SCAP complex in the ER in the presence of sterols, thus providing a more complete understanding of the control of proteolysis in this complex regulatory pathway. Sterols 168-175 insulin induced gene 1 Homo sapiens 67-74 12535518-3 2003 Here, we show that degradation of HMG CoA reductase is accelerated by the sterol-induced binding of its sterol-sensing domain to the ER protein insig-1. Sterols 104-110 insulin induced gene 1 Homo sapiens 144-151 12535518-6 2003 Insig-1 appears to play an essential role in the sterol-mediated trafficking of two proteins with sterol-sensing domains, HMG CoA reductase and SCAP. Sterols 49-55 insulin induced gene 1 Homo sapiens 0-7 12202038-0 2002 Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Sterols 41-48 insulin induced gene 1 Homo sapiens 76-83 12242332-6 2002 The combined actions of insig-1 and -2 permit feedback regulation of cholesterol synthesis over a wide range of sterol concentrations. Sterols 74-80 insulin induced gene 1 Homo sapiens 24-38 12242342-6 2002 These findings suggest that the INSIG-1 protein alters sterol balance by modulating SREBP processing jointly with SCAP. Sterols 55-61 insulin induced gene 1 Homo sapiens 32-39 12202038-1 2002 Using coimmunoprecipitation and tandem mass spectrometry, we identify INSIG-1 as an ER protein that binds the sterol-sensing domain of SREBP cleavage-activating protein (SCAP) and facilitates retention of the SCAP/SREBP complex in the ER. Sterols 110-116 insulin induced gene 1 Homo sapiens 70-77 12202038-3 2002 Sterols induce binding of SCAP to INSIG-1, as determined by blue native-PAGE, and this is correlated with the inhibition of SCAP exit from the ER. Sterols 0-7 insulin induced gene 1 Homo sapiens 34-41 12202038-4 2002 Overexpression of INSIG-1 increases the sensitivity of cells to sterol-mediated inhibition of SREBP processing. Sterols 64-70 insulin induced gene 1 Homo sapiens 18-25 12202038-6 2002 By facilitating sterol-dependent ER retention of SCAP, INSIG-1 plays a central role in cholesterol homeostasis. Sterols 16-22 insulin induced gene 1 Homo sapiens 55-62 33446483-2 2021 The key players in this pathway, Scap and Insig-1/2, are membrane-embedded sterol sensors. Sterols 75-81 insulin induced gene 1 Homo sapiens 42-51 26160948-2 2015 Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Sterols 89-95 insulin induced gene 1 Homo sapiens 0-22 26160948-2 2015 Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Sterols 89-95 insulin induced gene 1 Homo sapiens 24-31 26160948-2 2015 Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Sterols 147-154 insulin induced gene 1 Homo sapiens 0-22 26160948-2 2015 Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Sterols 147-154 insulin induced gene 1 Homo sapiens 24-31 23403031-2 2013 The ERAD of reductase slows a rate-limiting step in cholesterol synthesis and results from sterol-induced binding of its membrane domain to Insig-1 and the highly related Insig-2 protein. Sterols 57-63 insulin induced gene 1 Homo sapiens 140-147 23403031-5 2013 Sterols block this ERAD by inhibiting Insig-1 ubiquitination, whereas unsaturated fatty acids block the reaction by preventing the protein"s cytosolic dislocation. Sterols 0-7 insulin induced gene 1 Homo sapiens 38-45 23403031-9 2013 The ERAD of Insig-1 in S2 cells mimics the reaction that occurs in mammalian cells with regard to its inhibition by either sterols or unsaturated fatty acids. Sterols 123-130 insulin induced gene 1 Homo sapiens 12-19 22143767-2 2011 This degradation results from sterol-induced binding of reductase to the Insig-1 or Insig-2 proteins of ER membranes. Sterols 30-36 insulin induced gene 1 Homo sapiens 73-80 22143767-9 2011 The current results suggest that sterol-induced ubiquitination and proteasomal degradation of reductase is dictated by the complex interplay of at least four proteins: Insig-1, Insig-2, gp78, and Trc8. Sterols 33-39 insulin induced gene 1 Homo sapiens 168-175 30563842-1 2019 Insulin-induced gene 1 (INSIG1) regulates sterol synthesis by mediating the activation of sterol regulatory element-binding protein (SREBP) and the degradation of the HMG-CoA reductase (HMGCR). Sterols 42-48 insulin induced gene 1 Homo sapiens 0-22 30563842-1 2019 Insulin-induced gene 1 (INSIG1) regulates sterol synthesis by mediating the activation of sterol regulatory element-binding protein (SREBP) and the degradation of the HMG-CoA reductase (HMGCR). Sterols 42-48 insulin induced gene 1 Homo sapiens 24-30 24860107-1 2014 Accelerated endoplasmic reticulum (ER)-associated degradation (ERAD) of the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase results from its sterol-induced binding to ER membrane proteins called Insig-1 and Insig-2. Sterols 81-87 insulin induced gene 1 Homo sapiens 227-234 24025715-2 2013 Excess sterols cause the reductase to bind to ER membrane proteins called Insig-1 and Insig-2, which are carriers for the ubiquitin ligases gp78 and Trc8. Sterols 7-14 insulin induced gene 1 Homo sapiens 74-81