去泛素化酶在乳腺癌中的研究新进展

泛素-蛋白酶体系统(ubiquitin-proteasome-system,UPS)是控制蛋白质降解的主要系统,也是细胞基本活动的关键调节器。去泛素化酶(deubiquitinating enzymes,DUBs)是泛素-蛋白酶体系统的组成部分,主要参与调节蛋白质泛素化和去泛素化的动态平衡,对细胞增殖、信号转导、神经病变或肿瘤发生意义重大。不同的DUBs在乳腺癌中的作用不同,最新发现去泛素化酶BAP1、OTUD3、ATXN3L主要调节乳腺癌细胞增殖,某些DUBs小分子抑制剂可以间接诱导三阴性乳腺癌细胞凋亡。本文主要综述这三个DUBs及去泛素化酶抑制剂在乳腺癌中的研究新进展,为寻找新型的乳腺癌分子靶向药物提供理论依据。

New Advances in the Study on Deubiquitinating Enzymes in Breast Cancer Research*

ABSTRACT: The ubiquitin-proteasome-system (UPS) is the primary system for controlling protein degradation, and a key regulator of basic cellular processes as well. As a part of the UPS, deubiquitinating enzymes(DUBs) plays an important role in adjusting the dy- namic balance of protein ubiquitylation and deubiquitylation homeostasis, which is significant to cell proliferation, signal transduction, neuropathy and tumorigenesis. DUBs differ in their physiological actions to the breast cancer. Recent studies have found that the DUBs including BAP1, OTUD3 and ATXN3L are mainly responsible for the regulation of breast cancer cell proliferation, and the triple-nega- tive breast cancer cells can be indirectly induced apoptosis by some small-molecule DUBs inhibitors. In this review, we mainly summa- rizes the development of these three DUBs and DUBs inhibitors in breast cancer, in order to provide a new theoretical basis for finding new and effective molecular targeted drugs of breast cancer.