The pericentromeric protein shugoshin 2 cooperates with HSF1 in heat shock response and RNA Pol II recruitment
The pericentromeric protein shugoshin 2 cooperates with HSF1 in heat shock response and RNA Pol II recruitment
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DOI：
10.15252/embj.2019102566
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发表时间：
2019-12
期刊：
影响因子：
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通讯作者：
Ryosuke Takii;M. Fujimoto;M. Matsumoto;P. Srivastava;Arpit Katiyar;K. Nakayama;A. Nakai
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文献类型：
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作者：
Ryosuke Takii;M. Fujimoto;M. Matsumoto;P. Srivastava;Arpit Katiyar;K. Nakayama;A. Nakai
RNA聚合酶II（Pol II）向核心启动子的募集在基因的快速诱导期间受到高度调节。热休克时，热休克转录因子1（HSF 1）被激活并占据热休克基因启动子。启动子结合的HSF 1募集与Pol II相互作用的一般转录因子和介体，但Pol II募集的应激特异性机制尚不清楚。在这里，我们显示在比较分析的HSF 1旁系同源物和它们的突变体，HSF 1相互作用的pericentromeric衔接蛋白shugoshin 2（SGO 2）在小鼠细胞中的热休克过程中，在一种方式依赖于诱导磷酸化的HSF 1在丝氨酸326，和招聘SGO 2的HSP 70启动子。SGO 2介导的Pol II与低磷酸化C末端结构域的结合和募集促进HSP 70的表达，暗示SGO 2是促进HSF 1募集Pol II的共激活剂之一。此外，HSF 1-SGO 2复合物支持热休克条件下的细胞存活和蛋白质稳态的维持。这些结果证实了Pol II募集的蛋白毒性应激特异性机制，其由热休克反应期间HSF 1的磷酸化触发。
The recruitment of RNA polymerase II (Pol II) to core promoters is highly regulated during rapid induction of genes. In response to heat shock, heat shock transcription factor 1 (HSF1) is activated and occupies heat shock gene promoters. Promoter‐bound HSF1 recruits general transcription factors and Mediator, which interact with Pol II, but stress‐specific mechanisms of Pol II recruitment are unclear. Here, we show in comparative analyses of HSF1 paralogs and their mutants that HSF1 interacts with the pericentromeric adaptor protein shugoshin 2 (SGO2) during heat shock in mouse cells, in a manner dependent on inducible phosphorylation of HSF1 at serine 326, and recruits SGO2 to the HSP70 promoter. SGO2‐mediated binding and recruitment of Pol II with a hypophosphorylated C‐terminal domain promote expression of HSP70, implicating SGO2 as one of the coactivators that facilitate Pol II recruitment by HSF1. Furthermore, the HSF1‐SGO2 complex supports cell survival and maintenance of proteostasis in heat shock conditions. These results exemplify a proteotoxic stress‐specific mechanism of Pol II recruitment, which is triggered by phosphorylation of HSF1 during the heat shock response.