探索HERC2和NEDD4L HECT E3泛素连接酶亚家族在p53信号通路及DNA损伤反应中的作用

Mathieu Nicholas A, Levin Rafael H, Spratt Donald E

Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA, United States.

Front Oncol. 2021 Mar 31;11:659049. doi: 10.3389/fonc.2021.659049. eCollection 2021.

Cellular homeostasis is governed by the precise expression of genes that control the translation, localization, and termination of proteins. Oftentimes, environmental and biological factors can introduce mutations into the genetic framework of cells during their growth and division, and these genetic abnormalities can result in malignant transformations caused by protein malfunction. For example, p53 is a prominent tumor suppressor protein that is capable of undergoing more than 300 posttranslational modifications (PTMs) and is involved with controlling apoptotic signaling, transcription, and the DNA damage response (DDR). In this review, we focus on the molecular mechanisms and interactions that occur between p53, the HECT E3 ubiquitin ligases WWP1, SMURF1, HECW1 and HERC2, and other oncogenic proteins in the cell to explore how irregular HECT-p53 interactions can induce tumorigenesis.

细胞内稳态由控制蛋白质翻译、定位和终止的基因的精确表达所调控。通常，环境和生物因素在细胞生长和分裂过程中可将突变引入细胞的遗传框架，这些遗传异常可导致因蛋白质功能异常而引起的恶性转化。例如，p53是一种重要的肿瘤抑制蛋白，能够发生300多种翻译后修饰（PTM），并参与控制凋亡信号传导、转录和DNA损伤反应（DDR）。在本综述中，我们聚焦于p53、HECT E3泛素连接酶WWP1、SMURF1、HECW1和HERC2以及细胞中其他致癌蛋白之间发生的分子机制和相互作用，以探讨不规则的HECT-p53相互作用如何诱导肿瘤发生。