The role of HSF4 in proteostasis

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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.