Open AccessInhibition of tumor suppressor p73 by nerve growth factor receptor via chaperone-mediated autophagy
Author(s) -
Daniel Nguyen,
Kun Yang,
Lucia J. Chiao,
Yun Deng,
Xiang Zhou,
Zhen Zhang,
Shelya X. Zeng,
Hua Lu
Publication year - 2020
Publication title -
journal of molecular cell biology/journal of molecular cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.825
H-Index - 62
eISSN - 1674-2788
pISSN - 1759-4685
DOI - 10.1093/jmcb/mjaa017
Subject(s) - autophagy , microbiology and biotechnology , mediator , transcription factor , chaperone (clinical) , biology , regulator , receptor , cell cycle checkpoint , low affinity nerve growth factor receptor , suppressor , apoptosis , cancer research , cell cycle , chemistry , nerve growth factor , gene , biochemistry , medicine , pathology
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.