| First Author | Yoon K | Year | 2008 |
| Journal | Cell Death Differ | Volume | 15 |
| Issue | 4 | Pages | 730-8 |
| PubMed ID | 18202703 | Mgi Jnum | J:150997 |
| Mgi Id | MGI:3852627 | Doi | 10.1038/sj.cdd.4402304 |
| Citation | Yoon K, et al. (2008) TRAF6 deficiency promotes TNF-induced cell death through inactivation of GSK3beta. Cell Death Differ 15(4):730-8 |
| abstractText | TNF receptor-associated factor 6 (TRAF6) plays a key role in the regulation of innate immune responses by mediating signals from both TNF receptors (TNFRs) and interleukin-1 receptors (IL-1Rs)/Toll-like receptors (TLRs). Here, we define a new role for TRAF6 in antagonizing cell death during TNF signaling. In TRAF6-deficient 3T3 (T6(-/-) 3T3) cells, TNF stimulation leads to the accumulation of reactive oxygen species (ROS), which in turn results in prolonged c-Jun N-terminal kinase (JNK) activation and accelerated cell death. Furthermore, TNF-induced p65/RelA phosphorylation as well as transcriptional activity of nuclear factor-kappaB (NF-kappaB) was significantly downregulated in T6(-/-) 3T3 cells. Interestingly, TRAF6 deficiency leads to constitutive phosphorylation and inactivation of glycogen synthase kinase 3beta (GSK3beta). Restoration of GSK3beta activity through exogenous expression of a GSK3beta constitutive active form rescued cell death in TRAF6-null 3T3 cells. These data suggest a role for TRAF6 in the maintenance of cell survival by regulating GSK3beta activity in TNF signaling. |
