14-3-3ɛ蛋白与肿瘤发生发展关系的研究进展

庞海垚; 孟峻

doi:10.13481/j.1671-587X.20240234

吉林大学学报(医学版) ›› 2024, Vol. 50 ›› Issue (2) : 572 -578. DOI: 10.13481/j.1671-587X.20240234

综述

14-3-3ɛ蛋白与肿瘤发生发展关系的研究进展

庞海垚,孟峻

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Research progress in relationship between 14-3-3ɛ protein and occurrence and development of tumor

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摘要

14-3-3ε蛋白也被称为YWHAE蛋白，是属于14-3-3蛋白家族的一种小相对分子质量的蛋白质。不同于蛋白激酶，14-3-3ε蛋白在细胞内并不参与蛋白质磷酸化反应，而是通过形成特殊的二聚体结构并与特定的磷酸化蛋白质结合，调节蛋白质配体的活性和亚细胞定位，从而参与多种细胞生命活动的调节。目前，在多种肿瘤中均已发现14-3-3ε蛋白的异常表达，异常表达的14-3-3ε蛋白对蛋白质配体的调节效应改变，进而影响蛋白质配体的亚细胞定位和酶活性，导致肿瘤细胞发生发展和侵袭转移。14-3-3ε蛋白的二聚体结构是其在肿瘤发生发展过程中发挥生物学功能的重要结构基础，破坏这一二聚体结构可有效靶向攻击肿瘤细胞。现基于国内外对14-3-3ε蛋白的研究成果，针对14-3-3ε蛋白的结构、作用机制及其在胃癌、肝癌、皮肤癌和其他多种肿瘤中发生发展过程中的影响及作用机制进行综述。

Abstract

14-3-3ε protein， also known as YWHAE protein， is a member of the 14-3-3 protein family characterized by a small relative molecular weight. Unlike protein kinases， 14-3-3ε protein does not participate in protein phosphorylation within the cells； instead， it forms the unique dimer structures and binds to the specific phosphorylated proteins，thereby regulating the activity and subcellular localization of the protein ligands and playing a role in the regulation of various cellular activities. The aberrant expression of 14-3-3ε protein has been discovered in the numerous cancers. The altered regulatory effect of aberrantly expressed 14-3-3ε protein on its protein ligands can affect the ligands’ subcellular localization and enzymatic activity， leading to the development， invasion， and metastasis of the tumor cells. The dimer structure of 14-3-3ε protein is a critical structural basis for its biological functions in the tumor progression， and disrupting the dimer structure could be targeted to kill the tumor cells. This review is based on the domestic and international research findings on the 14-3-3ε protein and covers its structure，mechanism， and the impact and mechanisms during the development process of gastric cancer， liver cancer， skin cancer， and various other tumors.