Subcellular localization of the J-protein Sis1 regulates the heat shock response.

Subcellular localization of the J-protein Sis1 regulates the heat shock response.
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J蛋白SIS1的亚细胞定位调节热休克响应。

DOI:
10.1083/jcb.202005165
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发表时间:
2021-01-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Pincus D
Pincus D
中科院分区:
其他
文献类型:
--
作者:
Feder ZA;Ali A;Singh A;Krakowiak J;Zheng X;Bindokas VP;Wolfgeher D;Kron SJ;Pincus D

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费德、阿里等人。揭示出芽酵母的热休克反应(HSR)中内置了空间调节。热休克触发 J 蛋白 Sis1 重新定位,远离核质。核质中 Sis1 的缺失会从 Hsp70 介导的抑制中释放转录因子 Hsf1,从而激活 HSR。暴露于热休克的细胞会诱导保守的基因表达程序,即热休克反应(HSR),编码蛋白质稳态(蛋白质稳态)因子。热休克还会触发蛋白稳态因子形成亚细胞质量控制体,但这些空间结构与 HSR 之间的关系尚不清楚。在这里,我们展示了 J 蛋白 Sis1(伴侣 Hsp70 的辅助因子)的定位控制着酵母中的 HSR 激活。在非应激条件下,Sis1 集中在核质中,促进 Hsp70 与转录因子 Hsf1 结合,从而抑制 HSR。热激后,Sis1 与其他蛋白稳态因子形成一个跨越核仁和内质网表面的互连网络。我们认为 Sis1 定位到该网络会引导 Hsp70 活性远离核质中的 Hsf1,从而使 Hsf1 自由地诱导 HSR。通过这种方式,Sis1 将 HSR 激活与蛋白质稳态网络的空间组织结合起来。
Feder, Ali et al. reveal that spatial regulation is built into the heat shock response (HSR) in budding yeast. Heat shock triggers the J-protein Sis1 to relocalize away from the nucleoplasm. Loss of Sis1 in the nucleoplasm releases the transcription factor Hsf1 from Hsp70-mediated repression to activate the HSR. Cells exposed to heat shock induce a conserved gene expression program, the heat shock response (HSR), encoding protein homeostasis (proteostasis) factors. Heat shock also triggers proteostasis factors to form subcellular quality control bodies, but the relationship between these spatial structures and the HSR is unclear. Here we show that localization of the J-protein Sis1, a cofactor for the chaperone Hsp70, controls HSR activation in yeast. Under nonstress conditions, Sis1 is concentrated in the nucleoplasm, where it promotes Hsp70 binding to the transcription factor Hsf1, repressing the HSR. Upon heat shock, Sis1 forms an interconnected network with other proteostasis factors that spans the nucleolus and the surface of the endoplasmic reticulum. We propose that localization of Sis1 to this network directs Hsp70 activity away from Hsf1 in the nucleoplasm, leaving Hsf1 free to induce the HSR. In this manner, Sis1 couples HSR activation to the spatial organization of the proteostasis network.
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