Tootle Tina L, Rebay Ilaria
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Bioessays. 2005 Mar;27(3):285-98. doi: 10.1002/bies.20198.
Transcription factors provide nodes of information integration by serving as nuclear effectors of multiple signaling cascades, and thus elaborate layers of regulation, often involving post-translational modifications, modulating and coordinate activities. Such modifications can rapidly and reversibly regulate virtually all transcription factor functions, including subcellular localization, stability, interactions with cofactors, other post-translational modifications and transcriptional activities. Aside from analyses of the effects of serine/threonine phosphorylation, studies on post-translational modifications of transcription factors are only in the initial stages. In particular, the regulatory possibilities afforded by combinatorial usage of and competition between distinct modifications on an individual protein are immense, and with respect to large families of closely related transcription factors, offer the potential of conferring critical specificity. Here we will review the post-translational modifications known to regulate ETS transcriptional effectors and will discuss specific examples of how such modifications influence their activities to highlight emerging paradigms in transcriptional regulation.
转录因子作为多个信号级联反应的核效应器,提供信息整合节点,从而构建调控层次,这通常涉及翻译后修饰,以调节和协调各种活动。此类修饰几乎可以快速且可逆地调节所有转录因子的功能,包括亚细胞定位、稳定性、与辅因子的相互作用、其他翻译后修饰以及转录活性。除了对丝氨酸/苏氨酸磷酸化作用的分析之外,对转录因子翻译后修饰的研究尚处于初始阶段。特别是,单个蛋白质上不同修饰的组合使用及其之间的竞争所带来的调控可能性是巨大的,对于关系密切的转录因子大家族而言,这提供了赋予关键特异性的潜力。在此,我们将综述已知可调节ETS转录效应器的翻译后修饰,并讨论此类修饰如何影响其活性的具体实例,以突出转录调控中出现的新模式。