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KAT2A和KAT2B在癌症生物学中涉及的非组蛋白靶点。

Nonhistone targets of KAT2A and KAT2B implicated in cancer biology .

作者信息

Bondy-Chorney Emma, Denoncourt Alix, Sai Yuka, Downey Michael

机构信息

Department of Cellular and Molecular Medicine and Ottawa Institute of Systems Biology, 451 Smyth Rd., Ottawa, ON KIH 8M5, Canada.

出版信息

Biochem Cell Biol. 2019 Feb;97(1):30-45. doi: 10.1139/bcb-2017-0297. Epub 2018 Apr 19.

Abstract

Lysine acetylation is a critical post-translation modification that can impact a protein's localization, stability, and function. Originally thought to only occur on histones, we now know thousands of nonhistone proteins are also acetylated. In conjunction with many other proteins, lysine acetyltransferases (KATs) are incorporated into large protein complexes that carry out these modifications. In this review we focus on the contribution of two KATs, KAT2A and KAT2B, and their potential roles in the development and progression of cancer. Systems biology demands that we take a broad look at protein function rather than focusing on individual pathways or targets. As such, in this review we examine KAT2A/2B-directed nonhistone protein acetylations in cancer in the context of the 10 "Hallmarks of Cancer", as defined by Hanahan and Weinberg. By focusing on specific examples of KAT2A/2B-directed acetylations with well-defined mechanisms or strong links to a cancer phenotype, we aim to reinforce the complex role that these enzymes play in cancer biology.

摘要

赖氨酸乙酰化是一种关键的翻译后修饰,它能够影响蛋白质的定位、稳定性和功能。最初人们认为这种修饰仅发生在组蛋白上,而现在我们知道数千种非组蛋白也会发生乙酰化。赖氨酸乙酰转移酶(KATs)与许多其他蛋白质一起,被纳入到执行这些修饰的大型蛋白质复合物中。在本综述中,我们重点关注两种KATs,即KAT2A和KAT2B,以及它们在癌症发生和发展中的潜在作用。系统生物学要求我们从更广泛的角度看待蛋白质功能,而不是专注于个别途径或靶点。因此,在本综述中,我们根据Hanahan和Weinberg定义的10个“癌症标志”来研究癌症中KAT2A/2B介导的非组蛋白乙酰化。通过关注具有明确机制或与癌症表型有紧密联系的KAT2A/2B介导的乙酰化的具体例子,我们旨在强化这些酶在癌症生物学中所起的复杂作用。

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