Following recruitment to receptor, TRAF2 mediates K63-linked polyubiquitination of cIAP1 and cIAP2. In addition to being an adaptor that recruits cIAP1/2 and TRAF3 to the receptor TRAF2 is also an E3 that activates cIAP1/2, through their K63-linked ubiquitination. This K63-linked ubiquitination stimulates the K48-ubiquitin ligase function of cIAP1/2 and may impose a change in the substrate specificity of cIAP1/2. Thus, rather than ubiquitinating NIK, cIAP1/2 ubiquitinates TRAF3 leading to its degradation (Vallabhapurapu et al. 2008, Wallach & Kovalenko 2008).
Mahoney, DJ, Wang, Y, Shiba, T, Mak, TW, Yeh, WC, Cheng, G, Dempsey, PW, He, J, Cheung, HH, Korneluk, RG, Yang, X, Zarnegar, BJ
Zhang, W, Tseng, PH, Matsuzawa, A, Vignali, DA, Bergsagel, PL, Keats, JJ, Karin, M, Wang, H, Vallabhapurapu, S
transferase activity of Non-canonical NF-kB initiating TNFRSF memebers [plasma membrane]
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