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首页> 外文期刊>Molecular and Cellular Biology >Cdk8 Regulates Stability of the Transcription Factor Phd1 To Control Pseudohyphal Differentiation of Saccharomyces cerevisiae
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Cdk8 Regulates Stability of the Transcription Factor Phd1 To Control Pseudohyphal Differentiation of Saccharomyces cerevisiae

机译：Cdk8调节转录因子Phd1的稳定性，以控制酿酒酵母的假菌丝分化。

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The yeast Saccharomyces differentiates into filamentous pseudohyphae when exposed to a poor source of nitrogen in a process involving a collection of transcription factors regulated by nutrient signaling pathways. Phd1 is important for this process in that it regulates expression of most other transcription factors involved in differentiation and can induce filamentation on its own when overproduced. In this article, we show that Phd1 is an unstable protein whose degradation is initiated through phosphorylation by Cdk8 of the RNA polymerase II mediator subcomplex. Phd1 is stabilized by cdk8 disruption, and the naturally filamenting Σ1278b strain was found to have a sequence polymorphism that eliminates a Cdk8 phosphorylation site, which both stabilizes the protein and contributes to enhanced differentiation. In nitrogen-starved cells, PHD1 expression is upregulated and the Phd1 protein becomes stabilized, which causes its accumulation during differentiation. PHD1 expression is partially dependent upon Ste12, which was also previously shown to be destabilized by Cdk8-dependent phosphorylations, but to a significantly smaller extent than Phd1. These observations demonstrate the central role that Cdk8 plays in initiation of differentiation. Cdk8 activity is inhibited in cells shifted to limiting nutrient conditions, and we argue that this effect drives the initiation of differentiation through stabilization of multiple transcription factors, including Phd1, that cause activation of genes necessary for filamentous response.
机译：当酵母菌暴露于氮源不足的过程中，其分化为丝状假菌丝，该过程涉及一系列受营养信号通路调控的转录因子。 Phd1在此过程中很重要，因为它调节分化过程中涉及的大多数其他转录因子的表达，并且在过量生产时可自行诱导丝化。在本文中，我们显示Phd1是一种不稳定的蛋白质，其降解是通过RNA聚合酶II介体亚复合体的Cdk8磷酸化而引发的。 Phd1通过 cdk8 破坏而稳定，并且发现天然丝状Σ1278b菌株具有消除Cdk8磷酸化位点的序列多态性，这既稳定了蛋白质又有助于增强分化。在氮饥饿的细胞中， PHD1 表达上调，Phd1蛋白变得稳定，这导致其在分化过程中积累。 PHD1 的表达部分依赖于Ste12，Ste12先前也被Cdk8依赖的磷酸化所破坏，但程度明显低于Phd1。这些观察结果证明Cdk8在分化起始中起着核心作用。 Cdk8活性在转移到限制营养条件的细胞中受到抑制，并且我们认为这种作用通过多种转录因子（包括Phd1）的稳定化来驱动分化的启动，这些转录因子引起丝状反应所需基因的激活。

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