Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041, China.
J Proteome Res. 2012 May 4;11(5):2625-34. doi: 10.1021/pr201151a. Epub 2012 Apr 24.
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.
热休克因子（HSFs）对于调节细胞内的应激和热休克相关基因表达至关重要。HSFs 的活性主要受翻译后修饰（PTMs）的控制。例如，HSF1 上三个丝氨酸位点的基础磷酸化抑制热休克反应，而应激激活激酶对 HSF1 上其他几个丝氨酸和苏氨酸位点的过度磷酸化导致其激活，而 K80 上的乙酰化抑制其 DNA 结合能力。HSF2 上 K82 的 SUMO 化调节其 DNA 结合能力，而 HSF4B 上 K293 的 SUMO 化抑制其转录活性。随着蛋白质组学技术的进步，使用串联质谱（MS/MS）已经鉴定出各种 HSF 上的新型 PTM 位点，但这些 PTM 中的许多功能仍不清楚。然而，应该注意的是，这些新型 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。随后进行的功能分析，最终将有助于更好地理解这些 PTM 标记。基于 MS/MS 的蛋白质组学方法已成为生命科学领域 PTM 验证的金标准。在这里，将讨论最近关于人类 HSFs 的所有已知 PTM 及其功能的文献。
