...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Ser46 phosphorylation regulates p53-dependent apoptosis and replicative senescence.
【24h】

Ser46 phosphorylation regulates p53-dependent apoptosis and replicative senescence.

机译：Ser46磷酸化调节p53依赖的细胞凋亡和复制性衰老。

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

Posttranslational modification such as phosphorylation of p53 plays important roles in activating p53 responses to various cellular and genotoxic stresses. Cell line studies have shown that phosphorylation of Ser46 is correlated with the activation of p53 apoptotic activity. To address the physiological roles of Ser46 phosphorylation, we employed homologous recombination and LoxP/Cre-mediated deletion to introduce Ser46 to Ala missense mutation into the human p53 knock-in (HUPKI) allele in mice (p53hki(S46A)). p53 stabilization in response to various types of DNA damage is modestly reduced in p53hki(S46A) embryonic stem (ES) cells, mouse embryonic fibroblasts (MEFs) and thymocytes. In addition, p53-dependent apoptosis is partially impaired in p53hki(S46A) thymocytes and E1A/Ras-expressing mouse embryonic fibroblasts (MEFs) after DNA damage. Consistent with this finding, transcription of p53 target apoptotic genes is preferentially affected by S46A mutation after DNA damage. p53hki(S46A) MEFs proliferate and reach senescence normally but can be spontaneously immortalized more easily than wild type MEFs. In addition, p53hki(S46A) MEFs more readily escapes from Ras-induced senescence. Therefore, Ser46 phosphorylation activates p53-dependent apoptosis induced by DNA damage and cellular senescence induced by oncogenic stress.
机译：翻译后修饰（例如p53的磷酸化）在激活p53对各种细胞和遗传毒性应激的应答中起重要作用。细胞系研究表明，Ser46的磷酸化与p53细胞凋亡活性的激活有关。为了解决Ser46磷酸化的生理作用，我们采用了同源重组和LoxP / Cre介导的缺失，将Ser46的Ala错义突变引入小鼠的人p53敲入（HUPKI）等位基因（p53hki（S46A））。 p53hki（S46A）胚胎干细胞（ES），小鼠胚胎成纤维细胞（MEFs）和胸腺细胞中，响应各种DNA损伤的p53稳定程度有所降低。此外，DNA损伤后，p53hki（S46A）胸腺细胞和表达E1A / Ras的小鼠胚胎成纤维细胞（MEFs）中p53依赖的细胞凋亡被部分削弱。与该发现一致，DNA损伤后，p53靶细胞凋亡基因的转录优先受到S46A突变的影响。 p53hki（S46A）MEF可以正常增殖并达到衰老，但比野生型MEF更容易自发永生。此外，p53hki（S46A）MEF更容易从Ras诱导的衰老中逃脱。因此，Ser46磷酸化激活由DNA损伤诱导的p53依赖性凋亡和由致癌应激诱导的细胞衰老。

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