TRAF6-mediated regulation of the PI3 kinase (PI3K)-Akt-GSK3β cascade is required for TNF-induced cell survival

Kwiyeom Yoon; Eun Joo Jung; Soo Young Lee

doi:10.1016/j.bbrc.2008.04.007

TRAF6-mediated regulation of the PI3 kinase (PI3K)-Akt-GSK3β cascade is required for TNF-induced cell survival

Kwiyeom Yoon, Eun Joo Jung, Soo Young Lee

Department of Life Science

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

We recently demonstrated that the tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) helps maintenance of cell survival by regulating glycogen synthase kinase 3β (GSK3β) activity during TNF signaling. However, the molecular linkage between TRAF6 and GSK3β signaling is unknown. Herein, we showed that TRAF6 positively regulated cell survival by modulating PI3K-Akt-GSK3β 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 GSK3β phosphorylation. Importantly, PI3K inhibition rescued cell death in TRAF6-null 3T3 cells. These data suggested TRAF6 regulates TNF-mediated cell survival through PI3K-Akt-GSK3β cascades.

Original language	English
Pages (from-to)	118-121
Number of pages	4
Journal	Biochemical and Biophysical Research Communications
Volume	371
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2008.04.007
State	Published - 20 Jun 2008

Bibliographical note

Funding Information:
We thank Dr. Wen-Chen Yeh for providing TRAF2-deficient 3T3 cells. This work was supported in part by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006-C00309), and by NCRC program of MOST/KOSEF (Grant No. R15-2006-020-00000-0) through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. K.Y. was supported by BK21 fellowship.

Keywords

Akt
Cell survival
GSK3β
PI3 kinase
TNF
TRAF6

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title = "TRAF6-mediated regulation of the PI3 kinase (PI3K)-Akt-GSK3β cascade is required for TNF-induced cell survival",

abstract = "We recently demonstrated that the tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) helps maintenance of cell survival by regulating glycogen synthase kinase 3β (GSK3β) activity during TNF signaling. However, the molecular linkage between TRAF6 and GSK3β signaling is unknown. Herein, we showed that TRAF6 positively regulated cell survival by modulating PI3K-Akt-GSK3β 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 GSK3β phosphorylation. Importantly, PI3K inhibition rescued cell death in TRAF6-null 3T3 cells. These data suggested TRAF6 regulates TNF-mediated cell survival through PI3K-Akt-GSK3β cascades.",

keywords = "Akt, Cell survival, GSK3β, PI3 kinase, TNF, TRAF6",

author = "Kwiyeom Yoon and Jung, {Eun Joo} and Lee, {Soo Young}",

note = "Funding Information: We thank Dr. Wen-Chen Yeh for providing TRAF2-deficient 3T3 cells. This work was supported in part by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006-C00309), and by NCRC program of MOST/KOSEF (Grant No. R15-2006-020-00000-0) through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. K.Y. was supported by BK21 fellowship.",

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N1 - Funding Information: We thank Dr. Wen-Chen Yeh for providing TRAF2-deficient 3T3 cells. This work was supported in part by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006-C00309), and by NCRC program of MOST/KOSEF (Grant No. R15-2006-020-00000-0) through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. K.Y. was supported by BK21 fellowship.

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N2 - We recently demonstrated that the tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) helps maintenance of cell survival by regulating glycogen synthase kinase 3β (GSK3β) activity during TNF signaling. However, the molecular linkage between TRAF6 and GSK3β signaling is unknown. Herein, we showed that TRAF6 positively regulated cell survival by modulating PI3K-Akt-GSK3β 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 GSK3β phosphorylation. Importantly, PI3K inhibition rescued cell death in TRAF6-null 3T3 cells. These data suggested TRAF6 regulates TNF-mediated cell survival through PI3K-Akt-GSK3β cascades.

AB - We recently demonstrated that the tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) helps maintenance of cell survival by regulating glycogen synthase kinase 3β (GSK3β) activity during TNF signaling. However, the molecular linkage between TRAF6 and GSK3β signaling is unknown. Herein, we showed that TRAF6 positively regulated cell survival by modulating PI3K-Akt-GSK3β 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 GSK3β phosphorylation. Importantly, PI3K inhibition rescued cell death in TRAF6-null 3T3 cells. These data suggested TRAF6 regulates TNF-mediated cell survival through PI3K-Akt-GSK3β cascades.

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TRAF6-mediated regulation of the PI3 kinase (PI3K)-Akt-GSK3β cascade is required for TNF-induced cell survival

Abstract

Bibliographical note

Keywords

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