TNFAIP3-interacting Protein 1

The ABIN family (ABIN-1, -2, and -3) is a group of adaptor proteins that associate and cooperate with A20/TNFAIP3 (1), a ubiquitin editing protein that inhibits the key inflammatory transcription factor NF-kB (2-4). Mechanistically, A20 acts by regulating the ubiquitination of the kinase RIP, which leads to inhibition of the IKK complex (5). ABIN-1 (Naf1/TNIP1) was identified based on its binding to A20 (6), as well as the HIV protein Nef-1 (7). Overexpression of ABIN-1 inhibits NF-kB activation by a number of stimuli including TNF, IL-1, and LPS. It is widely expressed and can be induced by NF-kB, providing a negative feedback loop of NF-kB signaling. In addition to binding to A20, ABIN-1 can function on other key components of NF-kB signaling including IKKgamma/NEMO (8) and NF-kB family members p100 and p105 (9), and can also inhibit ERK signaling (10). Knockout mice of ABIN-1 are embryonic lethal, with fetal liver apoptosis, anemia and hypoplasia (11). ABIN-1 deficient cells are hypersensitive to TNF-mediated apoptosis.