Regulation of transcription factor activity by interconnected post-translational modifications.
Regulation of transcription factor activity by interconnected post-translational modifications.
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通过相互关联的翻译后修饰调节转录因子活性。
DOI：
10.1016/j.tips.2013.11.005
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发表时间：
2014-02
影响因子：
13.8
通讯作者：
Leid, Mark
中科院分区：
文献类型：
--
作者：
Filtz, Theresa M.;Vogel, Walter K.;Leid, Mark
转录因子占人类蛋白质组的7%以上，是细胞功能的守门人，将外部信号信息整合到基因表达程序中，在最基本的水平上重新配置细胞生理学。表面启动的细胞信号传导途径汇聚在转录因子上，用一系列翻译后修饰（PTM）来修饰这些蛋白质，这些修饰通常是相互依赖的，在时间、空间和组合功能上相关联。这些PTM协调转录因子在其整个生命周期中的每一项活动-从亚细胞定位到蛋白质-蛋白质相互作用，序列特异性DNA结合，转录调节活性和蛋白质稳定性-并在基因表达的表观遗传调节中发挥关键作用。转录因子的多种PTM也为开发治疗多种疾病的治疗剂提供了许多潜在的干预点。我们回顾了最常见的针对转录因子的翻译后修饰，重点关注最近关于个体因素的顺序和相关翻译后修饰的报道。
Transcription factors comprise just over 7% of the human proteome and serve as the gatekeepers of cellular function, integrating external signal information into gene expression programs that reconfigure cellular physiology at the most basic levels. Surface-initiated, cell signaling pathways converge on transcription factors, decorating these proteins with an array of post-translational modifications (PTMs) that are often interdependent, being linked in time, space, and combinatorial function. These PTMs orchestrate every activity of a transcription factor over its entire lifespan—from subcellular localization to protein–protein interactions, sequence-specific DNA binding, transcriptional regulatory activity, and protein stability—and play key roles in the epigenetic regulation of gene expression. The multitude of PTMs of transcription factors also offers numerous potential points of intervention for development of therapeutic agents to treat a wide spectrum of diseases. We review PTMs most commonly targeting transcription factors, focusing on recent reports of sequential and linked PTMs of individual factors.
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