TNF receptor-associated factor 2 (TRAF2) regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis [, ].TRAF2 is heavily regulated by ubiquitin signals. It has E3 ubiquitin-protein ligase activity and promotes K63-linked ubiquitination of target proteins. Alternatively, TRAF2 may be required for recruiting other E3 ligases, such as A20, to help processing and turnover. Furthermore, TRAF2 is regulated by both K63 and K48 type ubiquitin chains. K63 linkage may be mediated by TRAF2 auto-ubiquitination, and is required for TRAF2 activation. c-IAPl and Siah2 are known E3 ligases that can K48-ubiquitinate TRAF2 to target it for proteasome-dependent degradation [, , ]. TRAF2 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded β-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors [, ].
TNF receptor-associated factor 2 (TRAF2) regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis [, ].TRAF2 is heavily regulated by ubiquitin signals. It has E3 ubiquitin-protein ligase activity and promotes K63-linked ubiquitination of target proteins. Alternatively, TRAF2 may be required for recruiting other E3 ligases, such as A20, to help processing and turnover. Furthermore, TRAF2 is regulated by both K63 and K48 type ubiquitin chains. K63 linkage may be mediated by TRAF2 auto-ubiquitination, and is required for TRAF2 activation. c-IAPl and Siah2 are known E3 ligases that can K48-ubiquitinate TRAF2 to target it for proteasome-dependent degradation [, , ]. TRAF2 contains a RING finger domain, five zinc finger domains, and a TRAF domain.
