Title : Celastrol induces ubiquitin-dependent degradation of mTOR in breast cancer cells.

Pub. Date : 2018

PMID : 30588010






10 Functional Relationships(s)
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1 Celastrol induces ubiquitin-dependent degradation of mTOR in breast cancer cells. celastrol mechanistic target of rapamycin kinase Homo sapiens
2 Celastrol inhibits PI3K-Akt-mTOR signaling, which is frequently dysregulated in tumors and critical for tumor-cell proliferation and survival, but the underlying mechanisms are still not fully understood. celastrol mechanistic target of rapamycin kinase Homo sapiens
3 In the present study, we investigated detailed mechanisms of celastrol inhibition of mTOR signaling in breast cancer cells. celastrol mechanistic target of rapamycin kinase Homo sapiens
4 Second, we examined the effects of celastrol on mTOR phosphorylation and expression using Western blot. celastrol mechanistic target of rapamycin kinase Homo sapiens
5 Furthermore, we investigated the cause of mTOR downregulation by celastrol using immunoprecipitation assays. celastrol mechanistic target of rapamycin kinase Homo sapiens
6 Celastrol inhibited mTOR phosphorylation and induced mTOR ubiquitination, resulting in its proteasomal degradation. celastrol mechanistic target of rapamycin kinase Homo sapiens
7 Celastrol inhibited mTOR phosphorylation and induced mTOR ubiquitination, resulting in its proteasomal degradation. celastrol mechanistic target of rapamycin kinase Homo sapiens
8 Mechanistically, we found that mTOR is a client of Hsp90-Cdc37 chaperone complex, and celastrol disrupts mTOR interaction with chaperone Hsp90 while promoting mTOR association with cochaperone Cdc37. celastrol mechanistic target of rapamycin kinase Homo sapiens
9 Mechanistically, we found that mTOR is a client of Hsp90-Cdc37 chaperone complex, and celastrol disrupts mTOR interaction with chaperone Hsp90 while promoting mTOR association with cochaperone Cdc37. celastrol mechanistic target of rapamycin kinase Homo sapiens
10 Conclusion: Our study reveals that celastrol suppresses mTOR signaling, at least in part through regulating its association with chaperones and inducing its ubiquitination. celastrol mechanistic target of rapamycin kinase Homo sapiens