TNFAIP3 (A20) removes lysine-63 (K63)-linked ubiquitin chains from Receptor interacting protein (RIPK1), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex. The carboxy-terminal domain of A20 then functions as a ubiquitin ligase, polyubiquitinating RIPK1 with K48-linked ubiquitin chains, thereby targeting RIPK1 for proteasomal degradation (Wertz et al. 2004) which leads to termination of TNF- or LPS-mediated activation of NF-kappa-B.
Dixit, VM, Koonin, EV, Eby, M, Aravind, L, Ma, A, O'Rourke, KM, Baker, R, Boone, DL, Wertz, IE, Wu, P, Seshagiri, S, Zhou, H, Wiesmann, C
Lys63-specific deubiquitinase activity of TNFAIP3:K63polyUb-RIPK1 [cytosol]
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