NF-kappaB Signaling

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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-κB (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-κB activation by a number of stimuli including TNF, IL-1, and LPS. It is widely expressed and can be induced by NF-κB, providing a negative feedback loop of NF-κB signaling. In addition to binding to A20, ABIN-1 can function on other key components of NF-κB signaling including IKKγ/NEMO (8) and NF-κB 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.

1. Verstrepen, L. et al. (2009) Biochem Pharmacol 78, 105-14.
2. Beyaert, R. et al. (2000) Biochem Pharmacol 60, 1143-51.
3. Lee, E.G. et al. (2000) Science 289, 2350-4.
4. Dixit, V.M. et al. (1990) J Biol Chem 265, 2973-8.
5. Wertz, I.E. et al. (2004) Nature 430, 694-9.
6. Heyninck, K. et al. (1999) J Cell Biol 145, 1471-82.
7. Fukushi, M. et al. (1999) FEBS Lett 442, 83-8.
8. Mauro, C. et al. (2006) J Biol Chem 281, 18482-8.
9. Cohen, S. et al. (2009) Biochem Biophys Res Commun 389, 205-10.
10. Zhang, S. et al. (2002) Biochem Biophys Res Commun 297, 17-23.
11. Oshima, S. et al. (2009) Nature 457, 906-9.

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ABIN-1 Antibody

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