...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Murine FGF-inducible kinase is rapidly degraded via the nuclear ubiquitin-proteosome system when overexpressed in NIH 3T3 cells.
【24h】

Murine FGF-inducible kinase is rapidly degraded via the nuclear ubiquitin-proteosome system when overexpressed in NIH 3T3 cells.

机译：当在NIH 3T3细胞中过表达时，鼠FGF诱导型激酶通过核泛素-蛋白体系统迅速降解。

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

FGF-inducible kinase (Fnk) is a member of the polo-like kinase family of structurally-related serine/threonine protein kinases. These kinases appear to play critical roles in normal cell cycle progression and in the DNA damage response. In the case of Fnk, several reports indicate that this protein normally functions in cells as a stress-activated checkpoint kinase. However, when Fnk is ectopically overexpressed in cells, it likely becomes constitutively activated, and this promotes cell cycle arrest and apoptosis. In the present paper, we report that murine Fnk has a short half-life when transiently overexpressed in transfected NIH 3T3 fibroblasts. In contrast, when a kinase-deficient Fnk mutant protein, Fnk-K92M, is overexpressed in transfected cells, it is significantly more stable. We also found that Fnk-wild-type (WT) and Fnk-K92M are present in both the nucleus and cytoplasm of transfected cells and that Fnk nuclear export requires CRM1 function. Both of these proteins are degraded in cells via the nuclear ubiquitin-proteosome system; however, Fnk-K92M does not enter the nuclear compartment as efficiently as Fnk-WT and consequently it is significantly more stable. These results demonstrate that Fnk expression levels in transfected cells can be regulated by nuclear-cytoplasmic trafficking, ubiquitination, and proteosome-dependent degradation. Furthermore, our studies indicate that the downregulation of endogenous Fnk activity in stressed cells may occur, at least in part, by Fnk nuclear translocation and proteosomal degradation.
机译：FGF诱导激酶（Fnk）是与结构相关的丝氨酸/苏氨酸蛋白激酶的polo-like激酶家族的成员。这些激酶似乎在正常细胞周期进程和DNA损伤反应中起关键作用。对于Fnk，有几篇报道表明该蛋白在细胞中通常作为应激激活的检查点激酶起作用。但是，当Fnk在细胞中异位表达时，它很可能被组成性激活，从而促进细胞周期停滞和凋亡。在本文中，我们报道了在转染的NIH 3T3成纤维细胞中瞬时过表达时，鼠Fnk的半衰期很短。相反，当激酶缺陷的Fnk突变蛋白Fnk-K92M在转染的细胞中过表达时，它会更加稳定。我们还发现，转染细胞的细胞核和细胞质中均存在Fnk-wild型（WT）和Fnk-K92M，并且Fnk核输出需要CRM1功能。这两种蛋白都通过核泛素-蛋白体系统在细胞中降解;但是，Fnk-K92M不能像Fnk-WT那样有效地进入核舱，因此它的稳定性大大提高。这些结果表明，转染细胞中Fnk的表达水平可以通过核质运输，泛素化和蛋白体依赖性降解来调节。此外，我们的研究表明，应激细胞中内源性Fnk活性的下调可能至少部分是由Fnk核易位和蛋白体降解引起的。

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