Scientific background: |
TNF receptor-associated factor 6, also called E3 ubiquitin-protein ligase TRAF6 or RNF85, is a TRAF human protein. The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from, members of the TNF receptor superfamily. This gene is mapped to 11p12. This protein mediates signaling from members of the TNF receptor superfamily as well as the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/RANCE and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. |
References: |
1. Akiyama, T., Maeda, S., Yamane, S., Ogino, K., Kasai, M., Kajiura, F., Matsumoto, M., Inoue, J. Dependence of self-tolerance on TRAF6-directed development of thymic stroma. Science 308: 248-251, 2005.
2. King, C. G., Kobayashi, T., Cejas, P. J., Kim, T., Yoon, K., Kim, G. K., Chiffoleau, E., Hickman, S. P., Walsh, P. T., Turka, L. A., Choi, Y. TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis. Nature Med. 12: 1088-1092, 2006.
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