...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >MDMX Promotes Proteasomal Turnover of p21 at G1 and Early S Phases Independently of, but in Cooperation with, MDM2
【24h】

MDMX Promotes Proteasomal Turnover of p21 at G1 and Early S Phases Independently of, but in Cooperation with, MDM2

机译：MDMX独立于MDM2，但与MDM2合作促进G1和S期早期的p21蛋白酶体转化

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

摘要

We have shown previously that MDM2 promotes the degradation of the cyclin-dependent kinase inhibitor p21 through a ubiquitin-independent proteolytic pathway. Here we report that the MDM2 analog, MDMX, also displays a similar activity. MDMX directly bound to p21 and mediated its proteasomal degradation. Although the MDMX effect was independent of MDM2, they synergistically promoted p21 degradation when coexpressed in cells. This degradation appears to be mediated by the 26S proteasome, as MDMX and p21 bound to S2, one of the subunits of the 19S component of the 26S proteasome, in vivo. Conversely, knockdown of MDMX induced the level of endogenous p21 proteins that no longer cofractionated with 26S proteasome, resulting in G1 arrest. The level of p21 was low at early S phase but markedly induced by knocking down either MDMX or MDM2 in human cells. Ablation of p21 rescued the G1 arrest caused by double depletion of MDM2 and MDMX in p53-null cells. These results demonstrate that MDMX and MDM2 independently and cooperatively regulate the proteasome-mediated degradation of p21 at the G1 and early S phases.
机译：先前我们已经表明，MDM2通过不依赖泛素的蛋白水解途径促进细胞周期蛋白依赖性激酶抑制剂p21的降解。在这里，我们报告说MDM2类似物MDMX也显示了类似的活动。 MDMX直接与p21结合并介导其蛋白酶体降解。尽管MDMX的作用不依赖于MDM2，但当它们在细胞中共表达时，它们可以协同促进p21降解。这种降解似乎是由26S蛋白酶体介导的，因为MDMX和p21在体内与S2（26S蛋白酶体19S组分的亚基之一）结合。相反，敲低MDMX会诱导不再与26S蛋白酶体共分离的内源性p21蛋白水平，从而导致G 1 阻滞。 p21的水平在S期早期较低，但通过敲低人细胞中的MDMX或MDM2明显诱导。 p21的切除挽救了p53无效细胞中MDM2和MDMX的双重耗竭引起的G 1 停滞。这些结果表明，MDMX和MDM2在G 1 和早期S期独立和协同调节蛋白酶体介导的p21降解。

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