...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Transforming growth factor beta (TGFbeta)-induced apoptosis: the rise & fall of Bim.
【24h】

Transforming growth factor beta (TGFbeta)-induced apoptosis: the rise & fall of Bim.

机译：转化生长因子β（TGFbeta）诱导的细胞凋亡：Bim的兴衰。

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

Transforming growth factor beta (TGFbeta) regulates essential cellular functions such as cellular proliferation, differentiation and apoptosis. Multiple apoptotic mediators and signaling pathways have been implicated in TGFbeta-induced apoptosis. Bim, a BH3-only protein, is critical for apoptosis in a variety of cell types. In resting cells, BimEL expression levels, the major and most abundant isoform, are controlled by Erk1/2-mediated phosphorylation, which targets BimEL for ubiquitination and degradation. We previously reported that TGFbeta induces the expression of the pro-apoptotic protein Bim through a Smad3-dependent mechanism to induce cell death in B-lymphocytes. A number of studies have shown TGFbeta to cause transcriptional induction of Bim in many cell types. Recently, we demonstrated that, in addition to its transcriptional effects on Bim, TGFbeta induces a MAPK phosphatase (MKP), MKP2/DUSP4, to rapidly increase BimEL levels by inactivation of Erk1/2, resulting in dephosphorylation and escape of BimEL from ubiquitin-mediated degradation. Our findings are of importance not only in the context that we implicate TGFbeta to increase BimEL levels through both an immediate post-translational regulatory mechanism and a long-term effect through transcriptional induction, but also in the context of implicating MKPs as regulatory players in apoptosis. Here we summarize these recent findings and their significance to our understanding of how TGFbeta mediates apoptosis, and we explore the possible regulatory mechanisms controlling Bim expression levels.
机译：转化生长因子β（TGFbeta）调节细胞的基本功能，例如细胞增殖，分化和凋亡。 TGFβ诱导的细胞凋亡中涉及多个凋亡介体和信号通路。 Bim是仅BH3的蛋白质，对于多种细胞类型的凋亡至关重要。在静止细胞中，BimEL表达水平是主要和最丰富的同工型，受Erk1 / 2介导的磷酸化控制，磷酸化靶向BimEL进行泛素化和降解。我们以前报道过，TGFbeta通过Smad3依赖性机制诱导B细胞中的细胞死亡，从而诱导促凋亡蛋白Bim的表达。大量研究表明，TGFbeta在许多细胞类型中均可引起Bim的转录诱导。最近，我们证明，除了其对Bim的转录作用外，TGFbeta还诱导MAPK磷酸酶（MKP）MKP2 / DUSP4通过使Erk1 / 2失活而迅速增加BimEL水平，从而导致BimEL脱磷酸化并从遍在蛋白中逃逸。介导的降解。我们的发现不仅对我们暗示TGFbeta通过直接的翻译后调节机制以及通过转录诱导的长期作用来提高BimEL水平具有重要意义，而且在牵涉MKPs作为凋亡调控因子的情况下也具有重要意义。在这里，我们总结了这些最新发现及其对理解TGFbeta如何介导细胞凋亡的意义，并探讨了控制Bim表达水平的可能调控机制。

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