...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Regulation of SCF(SKP2) ubiquitin E3 ligase assembly and p27(KIP1) proteolysis by the PTEN pathway and cyclin D1.
【24h】

Regulation of SCF(SKP2) ubiquitin E3 ligase assembly and p27(KIP1) proteolysis by the PTEN pathway and cyclin D1.

机译：通过PTEN途径和细胞周期蛋白D1对SCF（SKP2）泛素E3连接酶装配和p27（KIP1）蛋白水解的调节。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The PTEN tumor suppressor functions as a phosphatase of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and negatively regulates the PI 3-kinase signaling pathway. Our previous studies showed that PTEN expression causes accumulation of cyclin-dependent kinase inhibitor p27(Kip1) and G(1) cell cycle arrest. Here, we show that PTEN negatively regulates expression of cyclin D1 and that cyclin D1 plays a unique role in p27 proteolysis. Coexpression of cyclin D1, but not cyclin E, is sufficient to restore p27 levels in PTEN-expressing cells. Conversely, loss of cyclin D1 by siRNA causes p27 accumulation. Silencing of the cyclin D1 gene or inhibition of the PI 3-kinase pathway prevents formation of the SCF(SKP2) complex, with a simultaneous increase in CUL1 binding to CAND1. CAND1-CUL1 binding is known to block the accessibility of CUL1 to SKP1 and (SKP2). We have found that CUL1 is less neddylated in cells that have lost cyclin D1 expression. Using an in vitro extract system, we found that the extracts prepared from cells lacking cyclin D1 have reduced activity to neddylate CUL1, in a manner similar to extracts from cells treated with a PI 3-kinase inhibitor or in G(0) resting cells. Consistently, the steady state levels of CUL1 neddylation were found lower under these conditions. Our studies reveal that PTEN/PI 3-kinase signaling and cyclin D1 control a novel pathway that regulates assembly of the SCF(SKP2) complex by modulating cullin neddylation and CAND1 binding at the G(1)/S cell cycle transition.
机译：PTEN肿瘤抑制剂起磷脂酰肌醇3,4,5-三磷酸（PIP3）的磷酸酶的作用，并负调控PI 3激酶的信号通路。我们以前的研究表明PTEN表达导致细胞周期蛋白依赖性激酶抑制剂p27（Kip1）和G（1）细胞周期停滞的积累。在这里，我们显示PTEN负调控细胞周期蛋白D1的表达，并且细胞周期蛋白D1在p27蛋白水解中起独特作用。共表达细胞周期蛋白D1，而不是细胞周期蛋白E，足以恢复表达PTEN的细胞中的p27水平。相反，siRNA丢失细胞周期蛋白D1会导致p27积累。沉默细胞周期蛋白D1基因或抑制PI 3-激酶通路可防止SCF（SKP2）复合物的形成，同时增加CUL1与CAND1的结合。已知CAND1-CUL1绑定会阻止CUL1对SKP1和（SKP2）的可访问性。我们已经发现，在细胞周期蛋白D1表达缺失的细胞中，CUL1的亚乙基化程度较低。使用体外提取物系统，我们发现从缺少细胞周期蛋白D1的细胞中制备的提取物具有降低的对Neddylate CUL1的活性，其方式类似于用PI 3-激酶抑制剂处理的细胞或G（0）静止细胞中的提取物。一致地，在这些条件下，发现CUL1醛基化的稳态水平较低。我们的研究表明，PTEN / PI 3-激酶信号和细胞周期蛋白D1控制通过调节cullin neddylation和CAND1结合在G（1）/ S细胞周期过渡来调节SCF（SKP2）复合体装配的新途径。

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