The nuclear factor NF-kB plays key roles in development and immunity. ABIN3 (A20-binding inhibitor of NF-kB activation 3), also known as TNFAIP3-interacting protein 3 (TNIP3), is a novel negative feedback regulator of LPS-induced NF-kB activation. ABIN3 is a 39 kDa protein that negatively regulates NF-kB activation in response to TNF and LPS. ABIN3 is highly expressed in brain, thymus, lymph node, lung and fetal liver, with low expression in kidney, bone marrow. Through its interaction with A20, ABIN3 interferes with TRAF2-mediated transactivation signals and NF-kB inhibition is mediated by the ABIN-homology domain 2. ABIN3 has been found to be induced by Listeria infection and can be slightly downregulated by dexamethasone. Enhanced expression of ABIN3 in monocytes is associated with sepsis. Thus, ABIN3 is an IL-10-induced gene product capable of attenuating NF-kB in human macrophages yet is inoperative in mice and represents a basis for species-specific differences in IL-10 actions. At least four isoforms of ABIN3 are known to exist.
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