Nuclear accumulation of p21Cip1 the onset of mitosis:: a role at the G2/M-phase transition
Nuclear accumulation of p21Cip1 the onset of mitosis:: a role at the G2/M-phase transition
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DOI：
10.1128/mcb.18.1.546
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发表时间：
1998-01-01
影响因子：
5.3
通讯作者：
Reed, SI
中科院分区：
文献类型：
--
作者：
Dulic, V;Stein, GH;Reed, SI
细胞周期在G1期因电离辐射或衰老而停滞，据信是由细胞周期蛋白依赖性激酶（Cdks）的抑制剂p21（Cip/Waf1/Sdi1）使G1期细胞周期蛋白 - 细胞周期蛋白依赖性激酶失活所引发的。我们提供的证据表明，除了对G1/S期转换施加负调控外，p21可能在有丝分裂起始阶段发挥作用。在未转化的成纤维细胞中，p21在接近G2/M期边界时在细胞核中短暂重新积累，与细胞周期蛋白B1的核转位同时发生，并与一部分细胞周期蛋白A - Cdk和细胞周期蛋白B1 - Cdk复合物结合。在p21水平较低的细胞中，如表达人乳头瘤病毒16型E6癌蛋白（该蛋白使p53功能失活）的成纤维细胞或肿瘤来源的细胞中，无法检测到细胞周期蛋白B1在有丝分裂前的核积累。此外，与野生型细胞相比，同步化的表达E6的成纤维细胞进入有丝分裂的速度加快，并且表现出更高的与细胞周期蛋白A和细胞周期蛋白B1相关的激酶活性。最后，来自p21（-/-）小鼠的原代胚胎成纤维细胞中，具有核内细胞周期蛋白B1的有丝分裂前细胞数量显著减少。这些数据表明，p21在G2期晚期促进一个短暂的停顿，这可能有助于细胞周期晚期检查点控制的实施。
Cell cycle arrest in G(1) in response to ionizing radiation or senescence is believed to be provoked by inactivation of G(1) cyclin-cyclin-dependent kinases (Cdks) by the Cdk inhibitor p21(Cip/Waf1/Sdi1). We provide evidence that in addition to exerting negative control of the G(1)/S phase transition, p21 may play a role at the onset of mitosis, In nontransformed fibroblasts, p21 transiently reaccumulates in the nucleus near the G(2)/M-phase boundary, concomitant with cyclin B1 nuclear translocation, and associates with a fraction of cyclin A-Cdk and cyclin B1-Cdk complexes, Premitotic nuclear accumulation of cyclin B1 is not detectable in cells with low p21 levels, such as fibroblasts expressing the viral human papillomavirus type 16 E6 oncoprotein, which functionally inactivates p53, or in tumor-derived cells, Moreover, synchronized E6-expressing fibroblasts show accelerated entry into mitosis compared to wild-type cells and exhibit higher cyclin A-and cyclin B1-associated kinase activities, Finally, primary embryonic fibroblasts derived from p21(-/-) mice have significantly reduced numbers of premitotic cells,vith nuclear cyclin B1, These data suggest that p21 promotes a transient pause late in G(2) that may contribute to the implementation of late cell cycle checkpoint controls.