Document Detail

TRAF6-mediated regulation of the PI3 kinase (PI3K)-Akt-GSK3beta cascade is required for TNF-induced cell survival.
MedLine Citation:
PMID:  18407828     Owner:  NLM     Status:  MEDLINE    
We recently demonstrated that the tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) helps maintenance of cell survival by regulating glycogen synthase kinase 3beta (GSK3beta) activity during TNF signaling. However, the molecular linkage between TRAF6 and GSK3beta signaling is unknown. Herein, we showed that TRAF6 positively regulated cell survival by modulating PI3K-Akt-GSK3beta cascades. In 3T3 cells lacking TRAF6, but not those lacking TRAF2, TNF stimulation led to prolonged hyperphosphorylation of Akt, which coincided with the activation of upstream PI3K. Pharmacologically blocking PI3K significantly inhibited Akt and GSK3beta phosphorylation. Importantly, PI3K inhibition rescued cell death in TRAF6-null 3T3 cells. These data suggested TRAF6 regulates TNF-mediated cell survival through PI3K-Akt-GSK3beta cascades.
Kwiyeom Yoon; Eun Joo Jung; Soo Young Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-11
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  371     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-09     Completed Date:  2008-06-03     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  118-21     Citation Subset:  IM    
Division of Life and Pharmaceutical Sciences, Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, 11-1, Daehyun-dong, Seoul 120-750, Republic of Korea.
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MeSH Terms
3T3 Cells
Apoptosis / genetics
Cell Survival* / genetics
Glycogen Synthase Kinase 3 / metabolism*
Mice, Mutant Strains
Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
TNF Receptor-Associated Factor 6 / genetics,  physiology*
Tumor Necrosis Factor-alpha / metabolism*,  pharmacology
Reg. No./Substance:
0/TNF Receptor-Associated Factor 6; 0/Tumor Necrosis Factor-alpha; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Proteins c-akt; EC synthase kinase 3 beta; EC Synthase Kinase 3

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