Abstract

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.

中文翻译：

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神经生长因子受体通过分子伴侣介导的自噬抑制肿瘤抑制因子 p73

摘要

肿瘤抑制因子 p73 是 p53 的同源物，能够诱导细胞周期停滞和细胞凋亡。在这里，我们将神经生长因子受体（NGFR、p75NTR 或 CD271）确定为一种新型的负 p73 调节剂。p73 激活 NGFR 转录，进而在负反馈回路中促进 p73 降解。NGFR 直接与 p73 中央 DNA 结合域结合并抑制 p73 转录活性以及 p73 介导的癌细胞凋亡。令人惊讶的是，我们通过伴侣介导的自噬 (CMA) 途径发现了 NGFR 促进 p73 降解的以前未知的机制。总的来说，我们的研究证明了 NGFR 通过促进其通过 CMA 降解来灭活 p73 活性的新致癌功能。