Inhibition of tumor suppressor p73 by nerve growth factor receptor via chaperone-mediated autophagy

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2020,（9）
• 所属期刊栏目: Articles
• 页码范围: 700-712
• 页数: 13页
• 语种: 英文
• DOI: 10.1093/jmcb/mjaa017

摘要

The tumor suppressr p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis.Here,we identify nerve growth factor receptor (NGFR,p75NTR,or CD271) as a novel negative p73 regulator.p73 activates NGFR transcription,which,in turn,promotes p73 degradation in a negative feedback loop.NGFR directly binds to p73 central DNA-binding domain and suppresses p73 transcriptional activity as well as p73-mediated apoptosis in cancer cells.Surprisingly,we uncover a previously unknown mechanism of NGFR-facilitated p73 degradation through the chaperone-mediated autophagy (CMA) pathway.Collectively,our studies demonstrate a new oncogenic function for NGFR in inactivating p73 activity by promoting its degradation through the CMA.