CELL-CYCLE INHIBITION BY INDEPENDENT CDK AND PCNA BINDING DOMAINS IN P21(CIP1)
CELL-CYCLE INHIBITION BY INDEPENDENT CDK AND PCNA BINDING DOMAINS IN P21(CIP1)
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DOI：
10.1038/375159a0
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发表时间：
1995-05-11
期刊：
影响因子：
64.8
通讯作者：
MASSAGUE, J
中科院分区：
文献类型：
--
作者：
LUO, Y;HURWITZ, J;MASSAGUE, J
抗有丝分裂信号对哺乳动物细胞周期的控制涉及p21（Cip 1/WAF 1）（参考文献1-4）、p27（Kip 1）（参考文献5、6）和p57（Kip 2）（参考文献7、8），这是一个结合并抑制S期起始所需的细胞周期蛋白依赖性激酶（CDK）的蛋白质家族。蛋白质p21还与DNA聚合酶6持续合成因子、增殖细胞核抗原（PCNA）结合，并抑制体外PCNA依赖性DNA复制（9，10）。p21的CDK和PCNA抑制活性在这里被证明是功能上独立的，并驻留在不同的蛋白质结构域。PCNA结合和抑制活性，这是没有观察到与p27或p57，驻留在C-末端结构域的p21，而CDK抑制活性驻留在保守的N-末端结构域的这些蛋白质。当在哺乳动物细胞中单独过表达时，CDK和PCNA抑制结构域阻止DNA复制，证明p21在体内作为细胞周期抑制剂的双重功能。
MAMMALIAN cell-cycle control by antimitogenic signals involves p21(Cip1/WAF1) (refs 1-4), p27(Kip1) (refs 5, 6) and p57(Kip2) (refs 7, 8), a family of proteins that bind to and inhibit cyclin-dependent kinases (CDKs) required for initiation of S phase. The protein p21 also binds to the DNA polymerase 6 processivity factor, proliferating-cell nuclear antigen (PCNA), and inhibits in vitro PCNA-dependent DNA replication(9,10). The CDK and PCNA inhibitory activities of p21 are shown here to be functionally independent and to reside in separate protein domains. The PCNA binding and inhibitory activities, which are not observed with p27 or p57, reside in the C-terminal domain of p21, whereas the CDK inhibitory activity resides in the conserved N-terminal domains of these proteins. When separately overexpressed in mammalian cells, the CDK and PCNA inhibitory domains prevent DNA replication, demonstrating a dual function of p21 as a cell-cycle inhibitor in vivo.