The Drosophila mitotic inhibitor Fruhstart specifically binds to the hydrophobic patch of cyclins
The Drosophila mitotic inhibitor Fruhstart specifically binds to the hydrophobic patch of cyclins
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DOI：
10.1038/sj.embor.7400948
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发表时间：
2007-05-01
期刊：
影响因子：
7.7
通讯作者：
Grosshans, Joerg
中科院分区：
文献类型：
--
作者：
Gawlinski, Pawel;Nikolay, Rainer;Grosshans, Joerg
细胞周期蛋白的疏水斑块与细胞周期蛋白依赖性激酶（Cdk）底物和p27型Cdk抑制剂相互作用。虽然这种相互作用被认为有助于不同的Cdk-细胞周期蛋白复合物的特异性，其在细胞周期的特定步骤中的作用尚未得到证实。在这里，我们表明，在果蝇的有丝分裂抑制剂Fruhstart（Frs）结合特异性和高亲和力的疏水补丁的细胞周期蛋白。与p27型Cdk抑制剂相反，Frs不与Cdk的催化中心形成稳定的相互作用，并允许通用模型底物（如组蛋白H1）磷酸化。与2.5倍强结合CycA比CycE在体外一致，异位表达的frs诱导内循环，以类似于先前报道的下调CycA或Cdk 1。我们建议，结合的Frs细胞周期蛋白块的疏水补丁干扰Cdk 1底物识别。
The hydrophobic patch of cyclins interacts with cyclin-dependent kinase (Cdk) substrates and p27-type Cdk inhibitors. Although this interaction is assumed to contribute to the specificity of different Cdk-Cyclin complexes, its role in specific steps of the cell cycle has not been demonstrated. Here, we show that in Drosophila the mitotic inhibitor Fruhstart (Frs) binds specifically and with high affinity to the hydrophobic patch of cyclins. In contrast to p27-type Cdk inhibitors, Frs does not form a stable interaction with the catalytic centre of Cdk and allows phosphorylation of generic model substrates, such as histone H1. Consistent with a 2.5 times stronger binding to CycA than to CycE in vitro, ectopic expression of frs induces endocycles, in a manner similar to that reported previously for down-regulation of CycA or Cdk1. We propose that binding of Frs to cyclins blocks the hydrophobic patch to interfere with Cdk1 substrate recognition.