Post-translational modification of human heat shock factors and their functions: a recent update by proteomic approach.
Post-translational modification of human heat shock factors and their functions: a recent update by proteomic approach.
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DOI：
10.1021/pr201151a
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发表时间：
2012-04
影响因子：
4.4
通讯作者：
Yan-Ming Xu;Dong-yang Huang;J. Chiu;Andy T. Y. Lau
中科院分区：
文献类型：
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作者：
Yan-Ming Xu;Dong-yang Huang;J. Chiu;Andy T. Y. Lau
热休克因子(HSF)在调节细胞内应激和热休克相关基因表达方面起着至关重要的作用。HSF的活性在很大程度上受翻译后修饰(PTM)的控制。例如，HSF1在三个丝氨酸位点上的基础磷酸化抑制了热休克反应，而应激激活的激酶使HSF1在其他几个丝氨酸和苏氨酸位点上过度磷酸化导致其激活，而K80上的乙酰化抑制了它的DNA结合能力。HSF2在K82上的苏莫化调节其与DNA的结合能力，而HSF4B在K293上的苏莫化抑制其转录活性。随着蛋白质组学技术的进步，利用串联质谱仪(MS/MS)已在多种HSF上发现了新的PTM位点，但其中许多PTM的功能尚不清楚。然而，应该指出的是，这些新的PTM位点的发现为这些PTM标记在体内的存在提供了必要的证据。在随后的功能分析之后，这最终将导致对这些PTM标记的更好理解。基于MS/MS的蛋白质组学方法正在成为生命科学领域中PTM验证的金标准。在这里，将讨论所有已知的关于人类HSF及其结果功能的PTM的最新文献。
Heat shock factors (HSFs) are vital for modulating stress and heat shock-related gene expression in cells. The activity of HSFs is controlled largely by post-translational modifications (PTMs). For example, basal phosphorylation of HSF1 on three serine sites suppresses the heat shock response, and hyperphosphorylation of HSF1 on several other serine and threonine sites by stress-activated kinases results in its activation, while acetylation on K80 inhibits its DNA-binding ability. Sumoylation of HSF2 on K82 regulates its DNA-binding ability, whereas sumoylation of HSF4B on K293 represses its transcriptional activity. With the advancement of proteomic technology, novel PTM sites on various HSFs have been identified with the use of tandem mass spectrometry (MS/MS), but the functions of many of these PTMs are still unclear. Yet, it should be noted that the discovery of these novel PTM sites provided the necessary evidence for the existence of these PTM marks in vivo. Followed by subsequent functional analysis, this would ultimately lead to a better understanding of these PTM marks. MS/MS-based proteomic approach is becoming a gold standard in PTM validation in the field of life science. Here, the recent literature of all known PTMs reported on human HSFs and the resulting functions will be discussed.