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Inhibition of tumor suppressor p73 by nerve growth factor receptor via chaperone-mediated autophagy
Daniel Nguyen1 , Kun Yang1 , Lucia Chiao1,3 , Yun Deng1,4 , Xiang Zhou1,5 , Zhen Zhang2 , Shelya X. Zeng1 , Hua Lu1,*
1Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA
2Department of Radiation Oncology, Shanghai Cancer Center, Department of Oncology, Shanghai Medical School, Fudan University, Shanghai 200032, China
3Present address: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
4Present address: Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
5Present address: Institute of Biomedical Sciences, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
*Correspondence to:Hua Lu , Email:hlu2@tulane.edu
J Mol Cell Biol, Volume 12, Issue 9, September 2020, 700-712,  https://doi.org/10.1093/jmcb/mjaa017

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.


Volume 12, Issue 9
September 2020