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

作　　者：Daniel Nguyen Kun Yang Lucia Chiao Yun Deng Xiang Zhou Zhen Zhang Shelya X.Zeng Hua Lu 

机构地区：[1]Department of Biochemistry and Molecular Biology,Tulane Cancer Center,Tulane University School of Medicine,New Orleans,LA 70112,USA [2]Department of Radiation Oncology,Shanghai Cancer Center,Department of Oncology,Shanghai Medical School,Fudan University,Shanghai 200032,China [3]Present address:Verna and Marrs McLean Department of Biochemistry and Molecular Biology,Baylor College of Medicine,Houston,TX 77030,USA [4]Present address:Department of Radiation Oncology,Shanghai Cancer Center,Fudan University,Shanghai 200032,China [5]Present address:Institute of Biomedical Sciences,Shanghai Cancer Center,Fudan University,Shanghai 200032,China

出　　处：《Journal of Molecular Cell Biology》2020年第9期700-712,共13页分子细胞生物学报（英文版）

基　　金：H.L. and S.X.Z.were supported in part by NIH-NCI grants(R01CA095441,R01CA17246 and R01CA127724).

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.

关 键 词：P73 NGFR chaperone-mediated autophagy Lamp2a HSPA8 

分 类 号：R979.1[医药卫生—药品]