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首页> 外文期刊>Cell cycle >Regulated expression of cofilin and the consequent regulation of p27(kip1) are essential for G(1) phase progression.
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Regulated expression of cofilin and the consequent regulation of p27(kip1) are essential for G(1) phase progression.

机译：cofilin的调节表达和相应的p27（kip1）调节对于G（1）阶段进展至关重要。

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Cofilin, a ubiquitously expressed actin binding protein, is responsible for the formation of the actin cytoskeleton and is indispensable for cell cycle control. However, the association between cofilin expression and the cell cycle remains to be elucidated. In this study, we found that the expression level of cofilin upregulated in G(1) phase-arrested confluent cells, while knockdown of cofilin expression by small interference RNA (siRNA) in these cells led to a reduction in the population of G(1) cells. To investigate the role of cofilin in the control of G(1) phase progression, a tet-on gene expression system was introduced to overexpress different concentrations of cofilin in cells. The results showed that G(1) phase progression was blocked following induction of exogenous cofilin. A survey of the cell cycle proteins controlling the G(1) phase progression revealed that the cyclin-dependent kinase inhibitor (CKI) p27(kip1) was the primary molecule induced by overexpressed cofilin in a time and dose dependent manner. Upregulated p27(kip1) repressed phosphorylation of the retinoblastoma protein (Rb) mediated by cyclin D1/CDK4 activity. Conversely, siRNA against p27(kip1) expression in the cofilin overexpressing cells released the G(1) phase arrest. Furthermore, we found that overexpression of cofilin led to induction of p27(kip1) gene promoter transactivation using luciferase reporter gene assay. This effect was associated with increase of p27(kip1) mRNA transiently. In addition, inhibition of threonine-187 phosphorylation of p27(kip1) protein for ubiquitinyl-proteasomal mediated degradation was also involved in upregulation of p27(kip1). These data suggest that cofilin expression and its regulation of p27(kip1) expression is important for the control of G(1) phase progression.
机译：肌动蛋白，一种普遍表达的肌动蛋白结合蛋白，负责肌动蛋白细胞骨架的形成，对于细胞周期控制是必不可少的。然而，cofilin表达与细胞周期之间的关联仍有待阐明。在这项研究中，我们发现在G（1）停滞的融合细胞中cofilin的表达水平上调，而这些细胞中小干扰RNA（siRNA）对cofilin表达的抑制导致G（1）种群的减少） 细胞。为了研究cofilin在G（1）阶段进展的控制中的作用，引入了tet-on基因表达系统以在细胞中过表达不同浓度的cofilin。结果表明，诱导外源性cofilin后，G（1）阶段进展被阻止。对控制G（1）相进程的细胞周期蛋白的调查显示，细胞周期蛋白依赖性激酶抑制剂（CKI）p27（kip1）是过表达cofilin诱导的主要分子，呈时间和剂量依赖性。上调的p27（kip1）抑制了由细胞周期蛋白D1 / CDK4活性介导的视网膜母细胞瘤蛋白（Rb）的磷酸化。相反，针对co27蛋白过表达细胞中p27（kip1）表达的siRNA释放了G（1）相停滞。此外，我们发现使用荧光素酶报告基因检测cofilin的过表达导致p27（kip1）基因启动子反式激活。这种作用与p27（kip1）mRNA的瞬时增加有关。此外，抑制苏氨酸187磷酸化p27（kip1）蛋白的泛素-蛋白酶体介导的降解也参与p27（kip1）的上调。这些数据表明cofilin表达及其对p27（kip1）表达的调节对于G（1）阶段进展的控制很重要。

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