Quantification of Hsp90 availability reveals differential coupling to the heat shock response.

Quantification of Hsp90 availability reveals differential coupling to the heat shock response.
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DOI:
10.1083/jcb.201803127
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发表时间:
2018-11-05
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Brandman O
Brandman O
中科院分区:
其他
文献类型:
--
作者:
Alford BD;Brandman O

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Alford和Brandman量化了Hsp90伴侣系统折叠其客户蛋白的能力,并描述了这种功能的丧失如何影响热休克反应。他们发现热休克反应通过独立监测多个伴侣系统的状态来响应蛋白质质量的各种缺陷。热休克反应(HSR)是一种保护性基因表达程序,在引起蛋白毒性应激的条件下被激活。虽然有人认为自由伴侣的可用性调节了HSR,但在应激条件下,伴侣的可用性和HSR从未被精确地量化。因此,伴侣的可用性在应激条件下如何变化以及这些变化在多大程度上驱动高铁是未知的。在本研究中,我们量化了多种应激条件下的Hsp90伴侣可用性和HSR。我们发现hsp90依赖性和非依赖性通路都能调节HSR,并且每种通路的作用因应激源的不同而有很大差异。此外,独立于Hsp90可用性调节HSR的应激源通过Hsp70伴侣来调节HSR。因此,HSR通过独立监测多个伴侣系统的状态来响应蛋白质质量的各种缺陷。
Alford and Brandman quantify the ability of the Hsp90 chaperone system to fold its client proteins and describe how loss of this functionality affects the heat shock response. They find that the heat shock response responds to diverse defects in protein quality by monitoring the state of multiple chaperone systems independently. 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.
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