...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >p14ARF triggers G2 arrest through ERK-mediated Cdc25C phosphorylation, ubiquitination and proteasomal degradation.
【24h】

p14ARF triggers G2 arrest through ERK-mediated Cdc25C phosphorylation, ubiquitination and proteasomal degradation.

机译：p14ARF通过ERK介导的Cdc25C磷酸化，泛素化和蛋白酶体降解来触发G2阻滞。

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 Cdc25C phosphatase is a key regulator of mitotic entry which activity is tightly regulated by phosphorylation. In response to DNA damage, phosphorylation at serine 216 induces the cytosolic retention of Cdc25C through 14-3-3 binding. We previously reported the ability of the p14ARF tumor suppressor to induce the accumulation of inactive phospho-Cdc25C(Ser216) protein as well as a decrease of Cdc25C steady state level and correlated these events with a p53-independent G2 arrest. The aim of this study was to investigate the cellular signaling pathways involved in this process. By using specific pharmacological inhibitors, we demonstrate that activation of the ERK1/2 MAP kinases pathway is involved in the p53-independent G2 checkpoint induced by p14ARF Moreover, we show that activated P-ERK1/2 bind and phosphorylate Cdc25C on its ser216 residue following p14ARF expression, thereby identifying Cdc25C as a new ERK1/2 target. Importantly, we further show that phosphorylation at Ser216 by phospho-ERK1/2 promotes Cdc25C ubiquitination and proteasomal degradation, suggesting that Cdc25C proteolysis is required for a sustained G2 arrest in response to p14ARF. Taken together, these results demonstrate that the MAPK ERK signaling pathway contributes to the p53-independent antiproliferative functions of p14ARF. Furthermore, they identify a new mechanism by which phosphorylation at serine 216 participates to Cdc25C inactivation.
机译：Cdc25C磷酸酶是有丝分裂进入的关键调节剂，其活性受磷酸化严格调节。响应DNA损伤，丝氨酸216的磷酸化通过14-3-3结合诱导Cdc25C的胞质保留。我们先前报道了p14ARF肿瘤抑制物诱导非活性磷酸Cdc25C（Ser216）蛋白积累以及Cdc25C稳态水平降低的能力，并将这些事件与p53独立的G2阻滞相关。这项研究的目的是调查参与此过程的细胞信号通路。通过使用特定的药理抑制剂，我们证明了ERK1 / 2 MAP激酶途径的激活与p14ARF诱导的p53独立的G2检查点有关。此外，我们证明了激活的P-ERK1 / 2在其ser216残基上结合并磷酸化Cdc25C p14ARF表达，从而将Cdc25C鉴定为新的ERK1 / 2靶标。重要的是，我们进一步表明，Ser216的磷酸化-ERK1 / 2磷酸化促进了Cdc25C泛素化和蛋白酶体降解，表明Cdc25C蛋白水解对于响应p14ARF的持续G2阻滞是必需的。两者合计，这些结果表明，MAPK ERK信号通路有助于p14ARF的p53独立的抗增殖功能。此外，他们确定了丝氨酸216磷酸化参与Cdc25C失活的新机制。

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