Transcription Regulation of HYPK by Heat Shock Factor 1

Abstract

HYPK (Huntingtin Yeast Partner K) was originally identified by yeast two-hybrid assay as an interactor of Huntingtin, the protein mutated in Huntington's disease. HYPK was characterized earlier as an intrinsically unstructured protein having chaperone-like activity in vitro and in vivo. HYPK has the ability of reducing rate of aggregate formation and subsequent toxicity caused by mutant Huntingtin. Further investigation revealed that HYPK is involved in diverse cellular processes and required for normal functioning of cells. In this study we observed that hyperthermia increases HYPK expression in human and mouse cells in culture. Expression of exogenous Heat Shock Factor 1 (HSF1), upon heat treatment could induce HYPK expression, whereas HSF1 knockdown reduced endogenous as well as heat-induced HYPK expression. Putative HSF1-binding site present in the promoter of human HYPK gene was identified and validated by reporter assay. Chromatin immunoprecipitation revealed in vivo interaction of HSF1 and RNA polymerase II with HYPK promoter sequence. Additionally, acetylation of histone H4, a known epigenetic marker of inducible HSF1 binding, was observed in response to heat shock in HYPK gene promoter. Overexpression of HYPK inhibited cells from lethal heat-induced death whereas knockdown of HYPK made the cells susceptible to lethal heat shock-induced death. Apart from elevated temperature, HYPK was also upregulated by hypoxia and proteasome inhibition, two other forms of cellular stress. We concluded that chaperone-like protein HYPK is induced by cellular stress and under transcriptional regulation of HSF1.

FAM172A modulates apoptosis and proliferation of colon cancer cells via STAT1 binding to its promoter

“…The process for ChIP was previously clarified ( 15 , 16 ). LoVo cells (1×10 6 ) were cultured for this experiment.…”

HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes

“…Interestingly, a significant number of HSF1 target genes (162, 2.81%) are active in all cell types examined so far, representing the ‘core’ HSF1 direct targets (Figure 2A and Table S3). The list of ‘core’ HSF1 targets includes several previously identified target genes of HSF1 (e.g., HYPK [27], STIP1 [28], BAG3 [28], JUN [29], and UBB [30]), as well as targets that have not yet been characterized in detail (e.g., CELSR1 , JMJD6, and TBL1X ).…”

Interaction of a Novel Chaperone PhLP2A With the Heat Shock Protein Hsp90

“…This may indicate that Hsf1, a main transcriptional regulator of heat shock response [Vihervaara and Sistonen, 2014], controls expression of PhLP2A. While Hsf1 is inactive under control conditions, during stress it becomes hyperphosphorylated and active [Guettouche et al, 2005;Das and Bhattacharyya, 2014;Sun et al, 2015]. Thus, in our experiments cells overexpressing Hsf1 were subjected to heat shock and we were able to observe a significant increase in the activity of the Pdcl3 gene promoter.…”