Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Hormone Action and Signal Transduction Program, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Mol Cell Biol. 2011 Dec;31(24):4858-73. doi: 10.1128/MCB.05631-11. Epub 2011 Oct 17.
Although discovered long ago, posttranslational phosphorylation of histones has been in the spotlight only recently. Information is accumulating almost daily on phosphorylation of histones and their roles in cellular physiology and human diseases. An extensive cross talk exists between phosphorylation and other posttranslational modifications, which together regulate various biological processes, including gene transcription, DNA repair, and cell cycle progression. Recent research on histone phosphorylation has demonstrated that nearly all histone types are phosphorylated at specific residues and that these modifications act as a critical intermediate step in chromosome condensation during cell division, transcriptional regulation, and DNA damage repair. As with all young fields, apparently conflicting and sometimes controversial observations about histone phosphorylations and their true functions in different species are found in the literature. Accumulating evidence suggests that instead of functioning strictly as part of a general code, histone phosphorylation probably functions by establishing cross talk with other histone modifications and serving as a platform for recruitment or release of effector proteins, leading to a downstream cascade of events. Here we extensively review published information on the complexities of histone phosphorylation, the roles of proteins recognizing these modifications and the resuting physiological outcome, and, importantly, future challenges and opportunities in this fast-moving field.
尽管组蛋白的翻译后磷酸化很久以前就被发现了，但直到最近才成为关注的焦点。几乎每天都有关于组蛋白磷酸化及其在细胞生理学和人类疾病中的作用的信息在积累。磷酸化与其他翻译后修饰之间存在广泛的相互作用，它们共同调节各种生物过程，包括基因转录、DNA 修复和细胞周期进程。最近对组蛋白磷酸化的研究表明，几乎所有类型的组蛋白都在特定残基上发生磷酸化，这些修饰在细胞分裂过程中的染色体浓缩、转录调控和 DNA 损伤修复中起着关键的中间步骤的作用。和所有的新兴领域一样，在文献中也发现了关于组蛋白磷酸化及其在不同物种中的真正功能的明显相互矛盾且有时相互矛盾的观察结果。越来越多的证据表明，组蛋白磷酸化可能不是作为一般密码的严格组成部分发挥作用，而是通过与其他组蛋白修饰建立交联，并作为募集或释放效应蛋白的平台，从而导致下游级联事件。在这里，我们广泛回顾了已发表的关于组蛋白磷酸化复杂性的信息，以及识别这些修饰的蛋白质的作用及其带来的生理结果，重要的是，在这个快速发展的领域中未来的挑战和机遇。
