• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Effects of p21Cip1/Waf1 at Both the G1/S and the G2/M Cell Cycle Transitions: pRb Is a Critical Determinant in Blocking DNA Replication and in Preventing Endoreduplication
【24h】

Effects of p21Cip1/Waf1 at Both the G1/S and the G2/M Cell Cycle Transitions: pRb Is a Critical Determinant in Blocking DNA Replication and in Preventing Endoreduplication

机译：p21Cip1 / Waf1在G1 / S和G2 / M细胞周期转换中的作用：pRb是阻止DNA复制和防止内复制的关键决定因素。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

It has been proposed that the functions of the cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p27Kip1 are limited to cell cycle control at the G1/S-phase transition and in the maintenance of cellular quiescence. To test the validity of this hypothesis, p21 was expressed in a diverse panel of cell lines, thus isolating the effects of p21 activity from the pleiotropic effects of upstream signaling pathways that normally induce p21 expression. The data show that at physiological levels of accumulation, p21, in addition to its role in negatively regulating the G1/S transition, contributes to regulation of the G2/M transition. Both G1- and G2-arrested cells were observed in all cell types, with different preponderances. Preponderant G1 arrest in response to p21 expression correlated with the presence of functional pRb. G2 arrest was more prominent in pRb-negative cells. The arrest distribution did not correlate with the p53 status, and proliferating-cell nuclear antigen (PCNA) binding activity of p21 did not appear to be involved, since p27, which lacks a PCNA binding domain, produced similar arrest Bs. In addition, DNA endoreduplication occurred in pRb-negative but not in pRb-positive cells, suggesting that functional pRb is necessary to prevent DNA replication in p21 G2-arrested cells. These results suggest that the primary target of the Cip/Kip family of inhibitors leading to efficient G1 arrest as well as to blockade of DNA replication from either G1 or G2 phase is the pRb regulatory system. Finally, the tendency of Rb-negative cells to undergo endoreduplication cycles when p21 is expressed may have negative implications in the therapy of Rb-negative cancers with genotoxic agents that activate the p53/p21 pathway.
机译：已经提出，细胞周期蛋白依赖性激酶抑制剂p21 Cip1 / Waf1 和p27 Kip1 的功能仅限于G 1 的细胞周期控制。 sub> / S相转变和维持细胞静止。为了检验该假设的有效性，p21在多种细胞系中表达，从而将p21活性的影响与正常诱导p21表达的上游信号通路的多效性隔离开来。数据表明，在生理水平的积累中，p21除了负调控G 1 / S过渡的作用外，还有助于调节G 2 / M。过渡。在所有细胞类型中均观察到G 1 -和G 2 停滞的细胞，优势不同。响应p21表达的主要G 1 停滞与功能性pRb的存在有关。在pRb阴性细胞中G 2 停滞更为明显。停滞分布与p53状态不相关，并且似乎不涉及p21的增殖细胞核抗原（PCNA）结合活性，因为缺少PCNA结合域的p27产生了类似的停滞Bs。此外，DNA核内复制在pRb阴性细胞中发生，而在pRb阳性细胞中则没有，这表明功能性pRb对于防止被p21 G 2 阻滞的细胞复制是必需的。这些结果表明，Cip / Kip抑制剂家族的主要靶标导致有效的G 1 阻滞以及从G 1 或G < sub> 2 阶段是pRb监管系统。最后，当表达p21时，Rb阴性细胞经历核内复制循环的趋势可能对通过激活p53 / p21途径的遗传毒性药物治疗Rb阴性癌症产生负面影响。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号