| First Author | Pathak S | Year | 2012 |
| Journal | EMBO J | Volume | 31 |
| Issue | 6 | Pages | 1394-404 |
| PubMed ID | 22307082 | Mgi Jnum | J:181911 |
| Mgi Id | MGI:5314426 | Doi | 10.1038/emboj.2012.8 |
| Citation | Pathak S, et al. (2012) O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release. EMBO J 31(6):1394-404 |
| abstractText | 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 kappaB and finally production of IL-6 and TNFalpha. This is one of the first examples of a single O-GlcNAc site on a signalling protein modulating a key innate immunity signalling pathway. |
