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Mediator Can Regulate Mitotic Entry and Direct Periodic Transcription in Fission Yeast

机译:介体可以调节裂变酵母中的有丝分裂进入和直接周期性转录

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Cdk8 is required for correct timing of mitotic progression in fission yeast. How the activity of Cdk8 is regulated is unclear, since the kinase is not activated by T-loop phosphorylation and its partner, CycC, does not oscillate. Cdk8 is, however, a component of the multiprotein Mediator complex, a conserved coregulator of eukaryotic transcription that is connected to a number of intracellular signaling pathways. We demonstrate here that other Mediator components regulate the activity of Cdk8 in vivo and thereby direct the timing of mitotic entry. Deletion of Mediator components Med12 and Med13 leads to higher cellular Cdk8 protein levels, premature phosphorylation of the Cdk8 target Fkh2, and earlier entry into mitosis. We also demonstrate that Mediator is recruited to clusters of mitotic genes in a periodic fashion and that the complex is required for the transcription of these genes. We suggest that Mediator functions as a hub for coordinated regulation of mitotic progression and cell cycle-dependent transcription. The many signaling pathways and activator proteins shown to function via Mediator may influence the timing of these cell cycle events.
机译:Cdk8是裂变酵母中有丝分裂进展正确时机所必需的。目前尚不清楚如何调节Cdk8的活性,因为该激酶不会被T环磷酸化激活,并且其伴侣CycC不会振荡。但是,Cdk8是多蛋白介体复合物的组成部分,它是一种保守的真核转录核心调节剂,与许多细胞内信号通路连接。我们在这里证明其他介体成分调节Cdk8在体内的活性,从而指导有丝分裂进入的时间。介体成分Med12和Med13的缺失会导致细胞Cdk8蛋白水平更高,Cdk8目标Fkh2的过早磷酸化以及更早进入有丝分裂状态。我们还证明,介体以周期性的方式被募集到有丝分裂基因的簇中,并且复杂是这些基因的转录所必需的。我们建议调解员作为有丝分裂进程和细胞周期依赖性转录的协调调控的枢纽。显示通过介体起作用的许多信号传导途径和激活蛋白可能会影响这些细胞周期事件的发生时间。

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