Zou J, Guo Y, Guettouche T, Smith D F, Voellmy R
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Florida 33101, USA.
Cell. 1998 Aug 21;94(4):471-80. doi: 10.1016/s0092-8674(00)81588-3.
Heat shock and other proteotoxic stresses cause accumulation of nonnative proteins that trigger activation of heat shock protein (Hsp) genes. A chaperone/Hsp functioning as repressor of heat shock transcription factor (HSF) could make activation of hsp genes dependent on protein unfolding. In a novel in vitro system, in which human HSF1 can be activated by nonnative protein, heat, and geldanamycin, addition of Hsp90 inhibits activation. Reduction of the level of Hsp90 but not of Hsp/c70, Hop, Hip, p23, CyP40, or Hsp40 dramatically activates HSF1. In vivo, geldanamycin activates HSF1 under conditions in which it is an Hsp90-specific reagent. Hsp90-containing HSF1 complex is present in the unstressed cell and dissociates during stress. We conclude that Hsp90, by itself and/or associated with multichaperone complexes, is a major repressor of HSF1.
热休克和其他蛋白毒性应激会导致非天然蛋白质的积累，从而触发热休克蛋白（Hsp）基因的激活。作为热休克转录因子（HSF）阻遏物发挥作用的伴侣蛋白/Hsp可能会使hsp基因的激活依赖于蛋白质的解折叠。在一种新型体外系统中，人HSF1可被非天然蛋白质、热和格尔德霉素激活，添加Hsp90会抑制激活。降低Hsp90的水平而非Hsp/c70、Hop、Hip、p23、CyP40或Hsp40的水平会显著激活HSF1。在体内，格尔德霉素在其作为Hsp90特异性试剂的条件下会激活HSF1。含Hsp90的HSF1复合物存在于未受应激的细胞中，并在应激过程中解离。我们得出结论，Hsp90自身和/或与多伴侣复合物相关联时，是HSF1的主要阻遏物。
