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...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.展开更多
基金H.L. and S.X.Z.were supported in part by NIH-NCI grants(R01CA095441,R01CA17246 and R01CA127724).
文摘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.
