Histone deacetylases (HDACs) are conserved enzymes that regulate many cellular processes by catalyzing the removal of acetyl groups from lysine residues on histones and non-histone proteins. As appropriate for proteins that occupy such an essential biological role, HDAC activities and functions are in turn highly regulated. Overwhelming evidence suggests that the dysregulation of HDACs plays a major role in many human diseases. The regulation of HDACs is achieved by multiple different mechanisms, including posttranslational modifications. One of the most common posttranslational modifications on HDACs is reversible phosphorylation. Many HDAC phosphorylations are context-dependent, occurring in specific tissues or as a consequence of certain stimuli. Additionally, whereas phosphorylation can regulate some HDACs in a non-specific manner, many HDAC phosphorylations result in specific consequences. Although some of these modifications support normal HDAC function, aberrations can contribute to disease development. Here we review and critically evaluate how reversible phosphorylation activates or deactivates HDACs and, thereby, regulates their many functions under various cellular and physiological contexts.

组蛋白去乙酰化酶 (HDAC) 是一种保守的酶，通过催化从组蛋白和非组蛋白上的赖氨酸残基中去除乙酰基来调节许多细胞过程。由于适用于具有这种重要生物学作用的蛋白质，HDAC 的活性和功能依次受到高度调节。压倒性的证据表明，HDAC 的失调在许多人类疾病中起着重要作用。HDAC 的调节是通过多种不同的机制实现的，包括翻译后修饰。HDAC 上最常见的翻译后修饰之一是可逆磷酸化。许多 HDAC 磷酸化是上下文相关的，发生在特定组织中或作为某些刺激的结果。此外，虽然磷酸化可以以非特异性方式调节一些 HDAC，许多 HDAC 磷酸化会导致特定的后果。尽管其中一些修饰支持正常的 HDAC 功能，但畸变可能会导致疾病发展。在这里，我们回顾并批判性地评估可逆磷酸化如何激活或停用 HDAC，从而在各种细胞和生理环境下调节它们的许多功能。