Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1
Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1
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DOI：
10.1158/0008-5472.can-03-2818
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发表时间：
2004-06-01
期刊：
影响因子：
11.2
通讯作者：
Friedman, SL
中科院分区：
文献类型：
--
作者：
Benzeno, S;Narla, G;Friedman, SL
Kruppel-like factor6(KLF6)是一种肿瘤抑制基因，在前列腺癌、结肠癌以及星形细胞胶质瘤中失活。在这里，我们确定KLF6通过与细胞周期蛋白D1的相互作用来调节生长抑制，导致视网膜母细胞瘤蛋白(Rb)在Ser(795)处的磷酸化减少。此外，KLF6的引入破坏了细胞周期蛋白D1-细胞周期蛋白依赖性蛋白激酶(CDK)4复合体，迫使p21(CIP/KIP)重新分布到CDK2上，从而促进G(1)期细胞周期停滞。我们的数据表明，KLF6与Rb通路融合，抑制细胞周期蛋白D1/CDK4的活性，导致生长抑制。
Kruppel-like factor 6 (KLF6) is a tumor suppressor gene inactivated in prostate and colon cancers, as well as in astrocytic gliomas. Here, we establish that KLF6 mediates growth inhibition through an interaction with cyclin D1, leading to reduced phosphorylation of the retinoblastoma protein (Rb) at Ser (795). Furthermore, introduction of KLF6 disrupts cyclin D1-cyclin-dependent kinase (cdk) 4 complexes and forces the redistribution of p21 (Cip/Kip) onto cdk2, which promotes G(1), cell cycle arrest. Our data suggest that KLF6 converges with the Rb pathway to inhibit cyclin D1/cdk4 activity, resulting in growth suppression.