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ARID1 蛋白:从转录和翻译后调控到致癌作用和潜在治疗靶点。

ARID1 proteins: from transcriptional and post-translational regulation to carcinogenesis and potential therapeutics.

机构信息

Department of Obstetrics & Gynecology & Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Department of Pharmacology & Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

出版信息

Epigenomics. 2021 May;13(10):809-823. doi: 10.2217/epi-2020-0414. Epub 2021 Apr 23.

Abstract

The ARID1 proteins are mutually exclusive subunits of the BRG1/BRM-associated factor (BAF) complexes that play an important role in chromatin remodeling and regulate many fundamental cell functions. The role of ARID1s is well defined as a tumor-suppressive. The cancer cells evolve different mechanisms to downregulate ARID1s and inactivate their functions. ARID1s are frequently mutated in human cancer. The recent findings of ARID1A/B downregulation at transcriptional and translational levels along with their low levels in human cancers indicate the significance of regulatory mechanisms of ARID1s in cancers. In this review, we present the current knowledge on the regulation and alterations of ARID1 protein expression in human cancers and indicate the importance of regulators of ARID1s as a prognostic marker and in potential therapeutic strategies.

摘要

ARID1 蛋白是 BRG1/BRM 相关因子 (BAF) 复合物的相互排斥的亚基,在染色质重塑中发挥重要作用,并调节许多基本的细胞功能。ARID1s 的作用被明确为肿瘤抑制因子。癌细胞通过不同的机制下调 ARID1s 并使其失活。ARID1s 在人类癌症中经常发生突变。最近发现 ARID1A/B 在转录和翻译水平下调,以及它们在人类癌症中的低水平,表明 ARID1s 在癌症中的调控机制具有重要意义。在这篇综述中,我们介绍了人类癌症中 ARID1 蛋白表达的调控和改变的最新知识,并指出了作为预后标志物和潜在治疗策略的 ARID1 调节剂的重要性。

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