期刊
DRUG RESISTANCE UPDATES
卷 13, 期 3, 页码 87-92出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.drup.2010.04.003
关键词
HDAC6; IRE1-JNK; ATF4; mTOR; LC3; Aggresome; Bortezomib
资金
- National Basic Research Program of China (973 Program) [2010CB529305]
- NIH [HL75826, HL83077]
- St. Baldrick's Foundation
- William Lawrence and Blanche Hughes Foundation
- Abbott Laboratories
- Genentech, Inc
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL075826, R01HL083077] Funding Source: NIH RePORTER
Macroautophagy and the ubiquitin-proteasome system are two complementary pathways for protein degradation. The former degrades long-lived proteins and damaged organelles while the later degrades short-lived proteins. Recent findings indicate that suppression of the ubiquitin-proteasome system by proteasome inhibitors induces macroautophagy through multiple pathways, including) accumulation of ubiquitinated proteins and activation of HDAC6; (2) activation of the IRE1-JNK pathway; (3) proteasomal stabilization of ATF4; (4) inhibition of mTOR complex 1 signaling; (5) reduced proteasomal degradation of LC3. Induction of macroautophagy attenuates the antitumor effect of proteasome inhibitors in various types of cancer. These findings suggest that inhibition of macroautophagy may represent a novel strategy to enhance cellular sensitivity to proteasome inhibition. (C) 2010 Elsevier Ltd. All rights reserved.
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