Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa.
Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa.
Biochem Biophys Res Commun. 2020 Jun 25;527(2):440-446. doi: 10.1016/j.bbrc.2020.04.072. Epub 2020 Apr 23.
Heat-shock factor 1 (HSF1) regulates the transcriptional response to stress and controls expression of molecular chaperones required for cell survival. Here we report that HSF1 is regulated by the abundance of the Hsp70-Hsp90 organizing protein (Hop/STIP1). HSF1 levels were significantly reduced in Hop-depleted HEK293T cells. HSF1 transcriptional activity at the Hsp70 promoter, and binding of a biotinylated HSE oligonucleotide under both basal and heat-shock conditions were significantly reduced. Hop-depleted HEK293T cells were more sensitive to the HSF1 inhibitor KRIBB11 and showed reduced short-term proliferation, and reduced long-term survival under basal and heat-shock conditions. HSF1 nuclear localization was reduced in response to heat-shock and the nuclear staining pattern in Hop-depleted cells was punctate. Taken together, these data suggest that Hop regulates HSF1 function under both basal and stress conditions through a mechanism involving changes in levels, activity and subcellular localization, and coincides with reduced cellular fitness.
热休克因子 1 (HSF1) 调节应激的转录反应，并控制细胞存活所需的分子伴侣的表达。在这里，我们报告 HSF1 受 Hsp70-Hsp90 组织蛋白 (Hop/STIP1) 的丰度调节。Hop 耗尽的 HEK293T 细胞中 HSF1 水平显著降低。在基础和热休克条件下，Hsp70 启动子上的 HSF1 转录活性以及生物素化 HSE 寡核苷酸的结合均显著降低。Hop 耗尽的 HEK293T 细胞对 HSF1 抑制剂 KRIBB11 更敏感，在基础和热休克条件下表现出短期增殖减少和长期存活减少。HSF1 的核定位在热休克后减少，并且在 Hop 耗尽的细胞中核染色模式呈点状。总之，这些数据表明 Hop 通过一种涉及水平、活性和亚细胞定位变化的机制在基础和应激条件下调节 HSF1 功能，并与细胞适应性降低相一致。
