First Author | Van Huffel S | Year | 2001 |
Journal | J Biol Chem | Volume | 276 |
Issue | 32 | Pages | 30216-23 |
PubMed ID | 11390377 | Mgi Jnum | J:76628 |
Mgi Id | MGI:2179873 | Doi | 10.1074/jbc.M100048200 |
Citation | Van Huffel S, et al. (2001) Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2. J Biol Chem 276(32):30216-23 |
abstractText | The nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of genes implicated in immune responses, inflammatory processes, and apoptotic cell death. The zinc finger protein A20 is a cellular inhibitor of NF-kappaB activation by various stimuli and plays a critical role in terminating NF-kappaB responses. The underlying mechanism for NF-kappaB inhibition by A20 is still unknown. A20 has been shown to interact with several proteins including tumor necrosis factor (TNF) receptor-associated factors 2 and 6, as well as the inhibitory protein of kappaB kinase (IKK) gamma protein. Here we report the cloning and characterization of ABIN-2, a previously unknown protein that binds to the COOH-terminal zinc finger domain of A20. NF-kappaB activation induced by TNF and interleukin-1 is inhibited by overexpression of ABIN-2. The latter also inhibits NF-kappaB activation induced by overexpression of receptor-interacting protein or TNF receptor-associated factor 2. In contrast, NF-kappaB activation by overexpression of IKKbeta or direct activators of the IKK complex, such as Tax, cannot be inhibited by ABIN-2. These results indicate that ABIN-2 interferes with NF-kappaB activation upstream of the IKK complex and that it might contribute to the NF-kappaB-inhibitory function of A20. |