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首页> 外文期刊>Molecular and Cellular Biology >Functional Analysis of the Cyclin-Dependent Kinase Inhibitor Pho81 Identifies a Novel Inhibitory Domain
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Functional Analysis of the Cyclin-Dependent Kinase Inhibitor Pho81 Identifies a Novel Inhibitory Domain

机译：细胞周期蛋白依赖性激酶抑制剂Pho81的功能分析确定了一个新型的抑制域。

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摘要

In response to phosphate limitation, Saccharomyces cerevisiae induces transcription of a set of genes important for survival. A phosphate-responsive signal transduction pathway mediates this response by controlling the activity of the transcription factor Pho4. Three components of this signal transduction pathway resemble those used to regulate the eukaryotic cell cycle: a cyclin-dependent kinase (CDK), Pho85; a cyclin, Pho80; and a CDK inhibitor (CKI), Pho81. Pho81 forms a stable complex with Pho80-Pho85 under both high- and low-phosphate conditions, but it only inhibits the kinase when cells are starved for phosphate. Pho81 contains six tandem repeats of the ankyrin consensus domain homologous to the INK4 family of mammalian CKIs. INK4 proteins inhibit kinase activity through an interaction of the ankyrin repeats and the CDK subunits. Surprisingly, we find that a region of Pho81 containing 80 amino acids C terminal to the ankyrin repeats is necessary and sufficient for Pho81's CKI function. The ankyrin repeats of Pho81 appear to have no significant role in Pho81 inhibition. Our results suggest that Pho81 inhibits Pho80-Pho85 with a novel motif.
机译：为了响应磷酸盐的限制，啤酒酵母（Saccharomyces cerevisiae）诱导了一系列对生存至关重要的基因的转录。磷酸盐反应性信号转导途径通过控制转录因子Pho4的活性来介导该反应。该信号转导途径的三个成分类似于用于调节真核细胞周期的成分：细胞周期蛋白依赖性激酶（CDK）Pho85;细胞周期蛋白Pho80; CDK抑制剂（CKI）Pho81。在高磷酸盐和低磷酸盐条件下，Pho81均可与Pho80-Pho85形成稳定的复合物，但仅当细胞饥饿时会抑制磷酸激酶。 Pho81包含与哺乳动物CKI的INK4家族同源的锚蛋白共有结构域的六个串联重复序列。 INK4蛋白通过锚蛋白重复序列​​和CDK亚基的相互作用抑制激酶活性。令人惊讶地，我们发现，锚蛋白重复序列​​的Cho末端含有80个氨基酸的Pho81区域对于Pho81的CKI功能是必要和充分的。 Pho81的锚蛋白重复在Pho81抑制中似乎没有重要作用。我们的结果表明，Pho81具有新颖的基序抑制Pho80-Pho85。

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