文章：

非典型MAPK ERK3在癌症生长与进展中的作用

Role of the Atypical MAPK ERK3 in Cancer Growth and Progression

原文发布日期：31 March 2024

DOI: 10.3390/cancers16071381

类型: Article

开放获取: 是

英文摘要：

Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) whose structural and regulatory features are distinct from those of conventional MAPKs, such as ERK1/2. Since its identification in 1991, the regulation, substrates and functions of ERK3 have remained largely unknown. However, recent years have witnessed a wealth of new findings about ERK3 signaling. Several important biological functions for ERK3 have been revealed, including its role in neuronal morphogenesis, inflammation, metabolism, endothelial cell tube formation and epithelial architecture. In addition, ERK3 has been recently shown to play important roles in cancer cell proliferation, migration, invasion and chemoresistance in multiple types of cancers. Furthermore, accumulating studies have uncovered various molecular mechanisms by which the expression level, protein stability and activity of ERK3 are regulated. In particular, several post-translational modifications (PTMs), including ubiquitination, hydroxylation and phosphorylation, have been shown to regulate the stability and activity of ERK3 protein. In this review, we discuss recent findings regarding biochemical and cellular functions of ERK3, with a main focus on its roles in cancers, as well as the molecular mechanisms of regulating its expression and activity.

摘要翻译： 

细胞外信号调节激酶3（ERK3）是一种非典型的丝裂原活化蛋白激酶（MAPK），其结构和调控特征与ERK1/2等经典MAPK存在显著差异。自1991年被发现以来，ERK3的调控机制、底物及功能在很大程度上仍属未知。然而近年来，关于ERK3信号通路的研究取得了大量新发现。研究揭示了ERK3在神经形态发生、炎症反应、代谢调控、内皮细胞管状结构形成及上皮组织构建等多个重要生物学过程中的作用。此外，最新研究表明ERK3在多种癌症的细胞增殖、迁移、侵袭及化疗耐药中发挥关键作用。越来越多的研究揭示了调控ERK3表达水平、蛋白稳定性及活性的多种分子机制，特别是泛素化、羟基化和磷酸化等翻译后修饰被证实可调控ERK3蛋白的稳定性与活性。本综述系统探讨了ERK3在生物化学及细胞功能方面的最新研究进展，重点阐述其在癌症中的作用，以及调控其表达和活性的分子机制。

原文链接：

Role of the Atypical MAPK ERK3 in Cancer Growth and Progression