A NEW REGULATORY MOTIF IN CELL-CYCLE CONTROL CAUSING SPECIFIC-INHIBITION OF CYCLIN-D/CDK4
A NEW REGULATORY MOTIF IN CELL-CYCLE CONTROL CAUSING SPECIFIC-INHIBITION OF CYCLIN-D/CDK4
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DOI：
10.1038/366704a0
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发表时间：
1993-12-16
期刊：
影响因子：
64.8
通讯作者：
BEACH, D
中科院分区：
文献类型：
--
作者：
SERRANO, M;HANNON, GJ;BEACH, D
真核细胞的分裂周期由称为细胞周期蛋白依赖性激酶 (CDK)1,2 的蛋白激酶家族调节。该家族各个成员的连续激活及其随后的关键底物磷酸化促进了细胞周期的有序进展3,4。 CDK4 和 D 型细胞周期蛋白形成的复合物与 G1 期 3-6 期间细胞增殖的控制密切相关。 CDK4 部分以多蛋白复合物的形式存在，其中包括 D 型细胞周期蛋白、增殖细胞核抗原和蛋白质 p21（参考文献 7-9）。 CDK4 分别与 M(r) 16K 蛋白结合，特别是在缺乏功能性视网膜母细胞瘤蛋白的细胞中。在这里，我们报告了人类 p16 互补 DNA 的分离，并证明 p16 与 CDK4 结合并抑制 CDK4/细胞周期蛋白 D 酶的催化活性。 p16 似乎与 CDK4、D 型细胞周期蛋白和视网膜母细胞瘤蛋白一起在调节反馈回路中发挥作用。
THE division cycle of eukaryotic cells is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs)1,2. The sequential activation of individual members of this family and their consequent phosphorylation of critical substrates promotes orderly progression through the cell cycle3,4. The complexes formed by CDK4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase3-6. CDK4 exists, in part, as a multi-protein complex with a D-type cyclin, proliferating cell nuclear antigen and a protein, p21 (refs 7-9). CDK4 associates separately with a protein of M(r) 16K, particularly in cells lacking a functional retinoblastoma protein9. Here we report the isolation of a human p16 complementary DNA and demonstrate that p16 binds to CDK4 and inhibits the catalytic activity of the CDK4/cyclin D enzymes. p16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retino-blastoma protein.