Macroautophagy modulates cellular response to proteasome inhibitors in cancer therapy DRUG RESISTANCE UPDATES Wu, W. K., Sakamoto, K. M., Milani, M., Aldana-Masankgay, G., Fan, D., Wu, K., Lee, C. W., Cho, C. H., Yu, J., Sung, J. J. 2010; 13 (3): 87-92

Abstract

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 (1) 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.

View details for DOI 10.1016/j.drup.2010.04.003

View details for Web of Science ID 000279649500004

View details for PubMedID 20462785