The role of HSF4 in proteostasis

在控制和应激条件下，热休克因子（HSFs）通过调节热休克蛋白（HSPs）和非hsp蛋白的表达来维持蛋白质稳态。在哺乳动物中，HSF家族成员由四个成员组成。其中HSF4是晶状体维持所必需的，HSF4突变与人类遗传性白内障有关。最近有研究表明，HSF4在其他组织或细胞类型中对应激的适应中起着重要作用。独特的是，HSF4组成了一个三聚体，可以与DNA结合。然而，HSF4的转录活性如何受到环境或生理信号的调控尚不清楚。为了找到调节HSF4活性的因素，我们进行了免疫沉淀分析，然后进行了质谱分析。此外，对这些因素进行了功能筛选。我们发现了一种促进HSF4磷酸化的新蛋白。我们提出了这个新因子调控HSF4的可能机制。

Heat shock factors (HSFs) maintain protein homeostasis through regulating expression of heat shock proteins (HSPs), and non-HSP proteins in both control and stressed conditions. HSF family members consist of four members in mammals. Among them, HSF4 is required for the maintenance of lens, and HSF4 mutation is associated with human inherited cataract. Recently, it reveals that HSF4 plays an important role in adaption to stresses in other tissues or cell types. Uniquely, HSF4 constitutively forms a trimer, which can bind to DNA. However, it is unclear how the transcriptional activity of HSF4 is regulated in response to environmental or physiological signals. To find factors that regulate HSF4 activity, we performed immunoprecipitation analysis, followed by mass spectrometry. Furthermore, these factors were functionally screened. We identified a novel protein that promotes phosphorylation of HSF4. We propose a possible mechanism of HSF4 regulation by this novel factor.