Department of Food and Nutrition, Keimyung University, Daegu, Korea.
Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA.
Diabetes Metab J. 2024 May;48(3):340-353. doi: 10.4093/dmj.2023.0174. Epub 2024 Mar 22.
Histone deacetylase 4 (HDAC4), a class IIa HDAC, has gained attention as a potential therapeutic target in treating inflammatory and metabolic processes based on its essential role in various biological pathways by deacetylating non-histone proteins, including transcription factors. The activity of HDAC4 is regulated at the transcriptional, post-transcriptional, and post-translational levels. The functions of HDAC4 are tissue-dependent in response to endogenous and exogenous factors and their substrates. In particular, the association of HDAC4 with non-histone targets, including transcription factors, such as myocyte enhancer factor 2, hypoxia-inducible factor, signal transducer and activator of transcription 1, and forkhead box proteins, play a crucial role in regulating inflammatory and metabolic processes. This review summarizes the regulatory modes of HDAC4 activity and its functions in inflammation, insulin signaling and glucose metabolism, and cardiac muscle development.
组蛋白去乙酰化酶 4(HDAC4)是一种 IIa 类 HDAC,由于其在通过去乙酰化非组蛋白蛋白(包括转录因子)来调节各种生物途径中的重要作用,已成为治疗炎症和代谢过程的潜在治疗靶点。HDAC4 的活性在转录、转录后和翻译后水平受到调节。HDAC4 的功能对组织具有依赖性,以响应内源性和外源性因素及其底物。特别是,HDAC4 与非组蛋白靶标的结合,包括转录因子,如肌细胞增强因子 2、缺氧诱导因子、信号转导和转录激活因子 1 和叉头框蛋白,在调节炎症和代谢过程中起着至关重要的作用。本综述总结了 HDAC4 活性的调节模式及其在炎症、胰岛素信号和葡萄糖代谢以及心肌发育中的功能。