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Publication : TRAF6-mediated regulation of the PI3 kinase (PI3K)-Akt-GSK3beta cascade is required for TNF-induced cell survival.

First Author  Yoon K Year  2008
Journal  Biochem Biophys Res Commun Volume  371
Issue  1 Pages  118-21
PubMed ID  18407828 Mgi Jnum  J:134685
Mgi Id  MGI:3789529 Doi  10.1016/j.bbrc.2008.04.007
Citation  Yoon K, et al. (2008) TRAF6-mediated regulation of the PI3 kinase (PI3K)-Akt-GSK3beta cascade is required for TNF-induced cell survival. Biochem Biophys Res Commun 371(1):118-21
abstractText  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.
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