期刊
AUTOPHAGY
卷 15, 期 9, 页码 1558-1571出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1586255
关键词
Autophagy; degradome; lysosome; proteome; translation
类别
资金
- Ragnar Soderberg Stiftelse
- Swedish Research Council (VR)
- Swedish Association for Medical Research (SSMF)
- Swedish Cancer Society
- Malin and Lennart Philipson Foundation
- Magnus Bergwalls Stiftelse
Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway of select soluble proteins. Nearly one-third of the soluble proteins are predicted to be recognized by this pathway, yet only a minor fraction of this proteome has been identified as CMA substrates in cancer cells. Here, we undertook a quantitative multiplex mass spectrometry approach to study the proteome of isolated lysosomes in cancer cells during CMA-activated conditions. By integrating bioinformatics analyses, we identified and categorized proteins of multiple cellular pathways that were specifically targeted by CMA. Beyond verifying metabolic pathways, we show that multiple components involved in select biological processes, including cellular translation, was specifically targeted for degradation by CMA. In particular, several proteins of the translation initiation complex were identified as bona fide CMA substrates in multiple cancer cell lines of distinct origin and we show that CMA suppresses cellular translation. We further show that the identified CMA substrates display high expression in multiple primary cancers compared to their normal counterparts. Combined, these findings uncover cellular processes affected by CMA and reveal a new role for CMA in the control of translation in cancer cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据