The adaptor protein TRIP6 antagonizes fas-induced apoptosis but promotes its effect on cell migration

Yun Ju Lai, Victor T.G. Lin, Ying Zheng, Etty N. Benveniste, Fang Tsyr Lin*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

29 引文 斯高帕斯(Scopus)

摘要

The Fas/CD95 receptor mediates apoptosis but is also capable of triggering nonapoptotic signals. However, the mechanisms that selectively regulate these opposing effects are not yet fully understood. Here we demonstrate that the activation of Fas or stimulation with lysophosphatidic acid (LPA) induces cytoskeletal reorganization, leading to the association of Fas with actin stress fibers and the adaptor protein TRIP6. TRIP6 binds to the cytoplasmic juxtamembrane domain of Fas and interferes with the recruitment of FADD to Fas. Furthermore, through physical interactions with NF-κB p65, TRIP6 regulates nuclear translocation and the activation of NF-κB upon Fas activation or LPA stimulation. As a result, TRIP6 antagonizes Fas-induced apoptosis and further enhances the antiapoptotic effect of LPA in cells that express high levels of TRIP6. On the other hand, TRIP6 promotes Fas-mediated cell migration in apoptosis-resistant glioma cells. This effect is regulated via the Src-dependent phosphorylation of TRIP6 at Tyr-55. As TRIP6 is overexpressed in glioblastomas, this may have a significant impact on enhanced NF-κB activity, resistance to apoptosis, and Fasmediated cell invasion in glioblastomas.

原文英語
頁(從 - 到)5582-5596
頁數15
期刊Molecular and cellular biology
30
發行號23
DOIs
出版狀態已發佈 - 2010 12月

ASJC Scopus subject areas

  • 分子生物學
  • 細胞生物學

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