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首页> 外文期刊>Molecular and Cellular Biology >Identification of Cdc37 as a Novel Regulator of the Stress-Responsive Mitogen-Activated Protein Kinase
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Identification of Cdc37 as a Novel Regulator of the Stress-Responsive Mitogen-Activated Protein Kinase

机译:Cdc37鉴定为应激反应的丝裂素活化蛋白激酶的新型调节剂。

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Eukaryotic cells utilize multiple mitogen-activated protein kinases (MAPKs) to transmit various extracellular stimuli to the nucleus. A subfamily of MAPKs that mediates environmental stress stimuli is also called stress-activated protein kinase (SAPK), which has crucial roles in cellular survival under stress conditions as well as inflammatory responses. Here we report that Cdc37, an evolutionarily conserved kinase-specific chaperone, is a positive regulator of Spc1 SAPK in the fission yeast Schizosaccharomyces pombe. Through a genetic screen, we have identified cdc37 as a mutation that compromises signaling through Spc1 SAPK. The Cdc37 protein physically interacts with Spc1, and the cdc37 mutation affects both the cellular level of the Spc1 protein and stress-induced Spc1 phosphorylation by Wis1 MAPK kinase (MAPKK). Consistently, expression of the stress response genes regulated by the Spc1 pathway is compromised in cdc37 mutant cells. On the other hand, a mutation in Hsp90, which often cooperates with Cdc37 in chaperoning protein kinases, does not affect Spc1 SAPK. These results suggest that Spc1 SAPK is a novel client protein for the Cdc37 chaperone, and the Cdc37 function is important to maintain the stability of the Spc1 protein and to facilitate stress signaling from Wis1 MAPKK to Spc1 SAPK.
机译:真核细胞利用多种促分裂原激活的蛋白激酶(MAPK)将各种细胞外刺激物传递至细胞核。介导环境应激刺激的MAPKs亚家族也称为应激激活蛋白激酶(SAPK),它在应激条件下的细胞存活以及炎症反应中起着至关重要的作用。在这里,我们报道Cdc37,一种进化上保守的激酶特异性伴侣,在裂殖酵母 Schizosaccharomyces pombe 中是Spc1 SAPK的正调节剂。通过遗传筛选,我们已鉴定出 cdc37 为突变,该突变破坏了通过Spc1 SAPK进行的信号传导。 Cdc37蛋白与Spc1发生物理相互作用,而 cdc37 突变既影响Spc1蛋白的细胞水平,又影响Wis1 MAPK激酶(MAPKK)胁迫诱导的Spc1磷酸化。一致地,在 cdc37 突变细胞中,受Spc1途径调控的应激反应基因的表达受到损害。另一方面,经常在伴侣蛋白激酶中与Cdc37协同作用的Hsp90突变不会影响Spc1 SAPK。这些结果表明,Spc1 SAPK是Cdc37分子伴侣的新型客体蛋白,而Cdc37功能对于维持Spc1蛋白的稳定性和促进从Wis1 MAPKK到Spc1 SAPK的应激信号传递非常重要。

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