Department of Biochemistry, Stanford University, Stanford, CA.
Department of Biochemistry, Stanford University, Stanford, CA
J Cell Biol. 2018 Nov 5;217(11):3809-3816. doi: 10.1083/jcb.201803127. Epub 2018 Aug 21.
The heat shock response (HSR) is a protective gene expression program that is activated by conditions that cause proteotoxic stress. While it has been suggested that the availability of free chaperones regulates the HSR, chaperone availability and the HSR have never been precisely quantified in tandem under stress conditions. Thus, how the availability of chaperones changes in stress conditions and the extent to which these changes drive the HSR are unknown. In this study, we quantified Hsp90 chaperone availability and the HSR under multiple stressors. We show that Hsp90-dependent and -independent pathways both regulate the HSR, and the contribution of each pathway varies greatly depending on the stressor. Moreover, stressors that regulate the HSR independently of Hsp90 availability do so through the Hsp70 chaperone. Thus, the HSR responds to diverse defects in protein quality by monitoring the state of multiple chaperone systems independently.
热休克反应（HSR）是一种保护性基因表达程序，由引起蛋白毒性应激的条件激活。虽然有人提出，游离伴侣蛋白的可用性调节 HSR，但在应激条件下，伴侣蛋白的可用性和 HSR 从未被精确地定量。因此，伴侣蛋白在应激条件下的变化情况以及这些变化在多大程度上驱动 HSR 尚不清楚。在这项研究中，我们定量了多种应激原下的 Hsp90 伴侣蛋白的可用性和 HSR。我们表明，Hsp90 依赖性和非依赖性途径都调节 HSR，而且每种途径的贡献因应激原而异。此外，独立于 Hsp90 可用性调节 HSR 的应激原，通过 Hsp70 伴侣蛋白来实现。因此，HSR 通过独立监测多个伴侣蛋白系统的状态来应对蛋白质质量的多种缺陷。
