细胞周期蛋白D1的过表达调节细胞周期蛋白依赖性激酶4的蛋白质合成。
Over-expression of cyclin D1 regulates Cdk4 protein synthesis.
作者信息
Parker M A, Deane N G, Thompson E A, Whitehead R H, Mithani S K, Washington M K, Datta P K, Dixon D A, Beauchamp R D
机构信息
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2730, USA.
出版信息
Cell Prolif. 2003 Dec;36(6):347-60. doi: 10.1046/j.1365-2184.2003.00290.x.
Increased Cdk4 expression occurs coincident with over-expression of cyclin D1 in many human tumours and tumourigenic mouse models. Here, we investigate both in vivo and in vitro the mechanism by which Cdk4 expression is regulated in the context of cyclin D1 over-expression. Cdk4 mRNA levels in cyclin D1-over-expressing tissue and cultured cells were unchanged compared with controls. In contrast, Cdk4 protein levels were increased in cyclin D1-over-expressing tissue and cells versus their respective controls. This increase was not due to altered protein stability, but appeared to be due to an increase in Cdk4 protein synthesis. We also performed immunoprecipitation and in vitro kinase assays to demonstrate an increase in cyclin D1-Cdk4 complex formation and associated kinase activity. Blocking cyclin D1 expression resulted in diminished Cdk4 protein but not mRNA levels. These findings suggest a mechanism by which Cdk4 expression is increased in the context of cyclin D1 over-expression during tumourigenesis.
在许多人类肿瘤和致瘤小鼠模型中，Cdk4表达增加与细胞周期蛋白D1的过表达同时出现。在此，我们在体内和体外研究了在细胞周期蛋白D1过表达的情况下Cdk4表达的调控机制。与对照相比，过表达细胞周期蛋白D1的组织和培养细胞中的Cdk4 mRNA水平没有变化。相反，与各自的对照相比，过表达细胞周期蛋白D1的组织和细胞中Cdk4蛋白水平增加。这种增加不是由于蛋白质稳定性改变，而是似乎由于Cdk4蛋白质合成增加。我们还进行了免疫沉淀和体外激酶测定，以证明细胞周期蛋白D1-Cdk4复合物形成和相关激酶活性增加。阻断细胞周期蛋白D1表达导致Cdk4蛋白水平降低，但mRNA水平未降低。这些发现提示了一种在肿瘤发生过程中细胞周期蛋白D1过表达情况下Cdk4表达增加的机制。
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