A class of their own: exploring the nondeacetylase roles of class IIa HDACs in cardiovascular disease.
A class of their own: exploring the nondeacetylase roles of class IIa HDACs in cardiovascular disease.
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他们自己的一类：探索 IIa 类 HDAC 在心血管疾病中的非脱乙酰酶作用。
DOI：
10.1152/ajpheart.00271.2016
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Menick,DonaldR
中科院分区：
文献类型：
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作者：
Wright,LillianneH;Menick,DonaldR
组蛋白去乙酰化酶（HDAC）在许多心血管生物学过程中起着不可或缺的作用，从转录和翻译调节到蛋白质稳定和定位。有18种已知的HDAC被分为4类，它们可以根据底物靶点、亚细胞定位和调节结合伴侣而不同。传统上已知HDAC能够从具有赖氨酸残基的组蛋白和非组蛋白蛋白中去除乙酰基。然而，尽管它们的命名和经典功能，在过去的十年中，许多研究小组的发现表明，非脱乙酰酶的作用存在于IIa类HDAC。这并不奇怪，因为IIa类HDAC具有例如相对差的脱乙酰酶能力，并且通常在特定的病理性和非病理性心脏事件时穿梭进出细胞核。本综述旨在巩固和阐明IIa类HDACs的假定非脱乙酰酶作用，并在可能的情况下，突出研究，提供证据，其非经典的作用，特别是在心血管疾病的背景下。最近人们对探索HDAC的药理学调节剂用于治疗心血管疾病和炎症的治疗性干预产生了极大的兴趣。因此，认真考虑HDAC的非酶和/或非脱乙酰酶作用可能是增强或消除病理学的关键是有意义的。这些非经典的HDAC功能可能会产生新的机制和药物发现的目标。
Histone deacetylases (HDACs) play integral roles in many cardiovascular biological processes ranging from transcriptional and translational regulation to protein stabilization and localization. There are 18 known HDACs categorized into 4 classes that can differ on the basis of substrate targets, subcellular localization, and regulatory binding partners. HDACs are classically known for their ability to remove acetyl groups from histone and nonhistone proteins that have lysine residues. However, despite their nomenclature and classical functions, discoveries from many research groups over the past decade have suggested that nondeacetylase roles exist for class IIa HDACs. This is not surprising given that class IIa HDACs have, for example, relatively poor deacetylase capabilities and are often shuttled in and out of nuclei upon specific pathological and nonpathological cardiac events. This review aims to consolidate and elucidate putative nondeacetylase roles for class IIa HDACs and, where possible, highlight studies that provide evidence for their noncanonical roles, especially in the context of cardiovascular maladies. There has been great interest recently in exploring the pharmacological regulators of HDACs for use in therapeutic interventions for treating cardiovascular diseases and inflammation. Thus it is of interest to earnestly consider nonenzymatic and or nondeacetylase roles of HDACs that might be key in potentiating or abrogating pathologies. These noncanonical HDAC functions may possibly yield new mechanisms and targets for drug discovery.