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O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release

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O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release. / Pathak, Shalini; Borodkin, Vladimir S.; Albarbarawi, Osama; Campbell, David G.; Ibrahim, Adel; van Aalten, Daan M. F. (Lead / Corresponding author).

In: EMBO Journal, Vol. 31, No. 6, 21.03.2012, p. 1394-1404.

Research output: Contribution to journalArticle

Harvard

Pathak, S, Borodkin, VS, Albarbarawi, O, Campbell, DG, Ibrahim, A & van Aalten, DMF 2012, 'O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release' EMBO Journal, vol 31, no. 6, pp. 1394-1404., 10.1038/emboj.2012.8

APA

Pathak, S., Borodkin, V. S., Albarbarawi, O., Campbell, D. G., Ibrahim, A., & van Aalten, D. M. F. (2012). O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release. EMBO Journal, 31(6), 1394-1404. 10.1038/emboj.2012.8

Vancouver

Pathak S, Borodkin VS, Albarbarawi O, Campbell DG, Ibrahim A, van Aalten DMF. O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release. EMBO Journal. 2012 Mar 21;31(6):1394-1404. Available from: 10.1038/emboj.2012.8

Author

Pathak, Shalini; Borodkin, Vladimir S.; Albarbarawi, Osama; Campbell, David G.; Ibrahim, Adel; van Aalten, Daan M. F. (Lead / Corresponding author) / O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release.

In: EMBO Journal, Vol. 31, No. 6, 21.03.2012, p. 1394-1404.

Research output: Contribution to journalArticle

Bibtex - Download

@article{17aa98db21424e3b92c40819a85c22cb,
title = "O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release",
author = "Shalini Pathak and Borodkin, {Vladimir S.} and Osama Albarbarawi and Campbell, {David G.} and Adel Ibrahim and {van Aalten}, {Daan M. F.}",
year = "2012",
doi = "10.1038/emboj.2012.8",
volume = "31",
number = "6",
pages = "1394--1404",
journal = "EMBO Journal",
issn = "0261-4189",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release

A1 - Pathak,Shalini

A1 - Borodkin,Vladimir S.

A1 - Albarbarawi,Osama

A1 - Campbell,David G.

A1 - Ibrahim,Adel

A1 - van Aalten,Daan M. F.

AU - Pathak,Shalini

AU - Borodkin,Vladimir S.

AU - Albarbarawi,Osama

AU - Campbell,David G.

AU - Ibrahim,Adel

AU - van Aalten,Daan M. F.

PY - 2012/3/21

Y1 - 2012/3/21

N2 - <p>Transforming growth factor (TGF)-beta-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as transforming growth factor-beta, tumour necrosis factor (TNF), interleukin-1 (IL-1) and wnt family ligands. TAK1 is found in complex with binding partners TAB1-3, phosphorylation and ubiquitination of which has been found to regulate TAK1 activity. In this study, we show that TAB1 is modified with N-acetylglucosamine (O-GlcNAc) on a single site, Ser395. With the help of a novel O-GlcNAc site-specific antibody, we demonstrate that O-GlcNAcylation of TAB1 is induced by IL-1 and osmotic stress, known inducers of the TAK1 signalling cascade. By reintroducing wild-type or an O-GlcNAc-deficient mutant TAB1 (S395A) into Tab1(-/-) mouse embryonic fibroblasts, we determined that O-GlcNAcylation of TAB1 is required for full TAK1 activation upon stimulation with IL-1/osmotic stress, for downstream activation of nuclear factor kappa B and finally production of IL-6 and TNF alpha. This is one of the first examples of a single O-GlcNAc site on a signalling protein modulating a key innate immunity signalling pathway. The EMBO Journal (2012) 31, 1394-1404. doi:10.1038/emboj. 2012.8; Published online 3 February 2012</p>

AB - <p>Transforming growth factor (TGF)-beta-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro-inflammatory cytokines such as transforming growth factor-beta, tumour necrosis factor (TNF), interleukin-1 (IL-1) and wnt family ligands. TAK1 is found in complex with binding partners TAB1-3, phosphorylation and ubiquitination of which has been found to regulate TAK1 activity. In this study, we show that TAB1 is modified with N-acetylglucosamine (O-GlcNAc) on a single site, Ser395. With the help of a novel O-GlcNAc site-specific antibody, we demonstrate that O-GlcNAcylation of TAB1 is induced by IL-1 and osmotic stress, known inducers of the TAK1 signalling cascade. By reintroducing wild-type or an O-GlcNAc-deficient mutant TAB1 (S395A) into Tab1(-/-) mouse embryonic fibroblasts, we determined that O-GlcNAcylation of TAB1 is required for full TAK1 activation upon stimulation with IL-1/osmotic stress, for downstream activation of nuclear factor kappa B and finally production of IL-6 and TNF alpha. This is one of the first examples of a single O-GlcNAc site on a signalling protein modulating a key innate immunity signalling pathway. The EMBO Journal (2012) 31, 1394-1404. doi:10.1038/emboj. 2012.8; Published online 3 February 2012</p>

UR - http://www.scopus.com/inward/record.url?scp=84858795203&partnerID=8YFLogxK

U2 - 10.1038/emboj.2012.8

DO - 10.1038/emboj.2012.8

M1 - Article

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 6

VL - 31

SP - 1394

EP - 1404

ER -

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