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

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5582-5596
Number of pages15
JournalMolecular and cellular biology
Volume30
Issue number23
DOIs
Publication statusPublished - 2010 Dec 1

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Cell Movement
Apoptosis
Glioblastoma
Proteins
CD95 Antigens
Stress Fibers
Glioma
Actins
Phosphorylation
lysophosphatidic acid

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The adaptor protein TRIP6 antagonizes fas-induced apoptosis but promotes its effect on cell migration. / Lai, Yun Ju; Lin, Victor T.G.; Zheng, Ying; Benveniste, Etty N.; Lin, Fang Tsyr.

In: Molecular and cellular biology, Vol. 30, No. 23, 01.12.2010, p. 5582-5596.

Research output: Contribution to journalArticle

Lai, Yun Ju ; Lin, Victor T.G. ; Zheng, Ying ; Benveniste, Etty N. ; Lin, Fang Tsyr. / The adaptor protein TRIP6 antagonizes fas-induced apoptosis but promotes its effect on cell migration. In: Molecular and cellular biology. 2010 ; Vol. 30, No. 23. pp. 5582-5596.
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