Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress
Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress
复制标题
酵母 Hsp70 的快速脱乙酰化介导细胞对热应激的反应。
DOI：
10.1038/s41598-019-52545-3
复制
发表时间：
2019-11-07
影响因子：
4.6
通讯作者：
Truman，Andrew W.
中科院分区：
文献类型：
--
作者：
Xu，Linan;Nitika，.;Truman，Andrew W.
HSP70是一种高度保守的分子伴侣，对新蛋白质和变性蛋白质的折叠至关重要。虽然传统的模型认为细胞通过上调可诱导的热休克蛋白来应对压力，但这种反应相对缓慢，并受到转录和翻译机制的限制。最近的研究已经确定了Hsp70上的一些翻译后修饰(PTM)，这些修饰可以微调其功能。我们利用质谱仪来确定酵母Hsp70(Ssa1)在热休克时是否有不同的修饰。我们在SSA1、K86、K185、K354和K562上发现了四个赖氨酸残基，它们在热激反应中被去乙酰化。这些位点的突变导致辅助伴侣和客户蛋白的Hsp70相互作用网络的实质性重塑，同时保留了基本的伴侣功能。这些残基上的乙酰化/去乙酰化改变了其他热休克诱导的伴侣蛋白的表达，并直接影响HSF1的活性。综上所述，我们的数据表明，细胞可能有能力通过Hsp70去乙酰化对热应激做出快速反应，然后是较慢的、更传统的转录反应。
Hsp70 is a highly conserved molecular chaperone critical for the folding of new and denatured proteins. While traditional models state that cells respond to stress by upregulating inducible HSPs, this response is relatively slow and is limited by transcriptional and translational machinery. Recent studies have identified a number of post-translational modifications (PTMs) on Hsp70 that act to fine-tune its function. We utilized mass spectrometry to determine whether yeast Hsp70 (Ssa1) is differentially modified upon heat shock. We uncovered four lysine residues on Ssa1, K86, K185, K354 and K562 that are deacetylated in response to heat shock. Mutation of these sites cause a substantial remodeling of the Hsp70 interaction network of co-chaperone partners and client proteins while preserving essential chaperone function. Acetylation/deacetylation at these residues alter expression of other heat-shock induced chaperones as well as directly influencing Hsf1 activity. Taken together our data suggest that cells may have the ability to respond to heat stress quickly though Hsp70 deacetylation, followed by a slower, more traditional transcriptional response.