Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Base Sequence, Blotting, Northern, Blotting, Western, Carrier Proteins, Cell Line, Cloning, Molecular, DNA, Complementary, Enzyme Activation, Enzyme Inhibitors, Humans, I-kappa B Kinase, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, NF-kappa B, Nuclear Proteins, Plasmids, Precipitin Tests, Protein Binding, Protein-Serine-Threonine Kinases, Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6, Tetradecanoylphorbol Acetate, Tissue Distribution, Transfection, Two-Hybrid System Techniques, Zinc Fingers
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Base Sequence, Blotting, Northern, Blotting, Western, Carrier Proteins, Cell Line, Cloning, Molecular, DNA, Complementary, Enzyme Activation, Enzyme Inhibitors, Humans, I-kappa B Kinase, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, NF-kappa B, Nuclear Proteins, Plasmids, Precipitin Tests, Protein Binding, Protein-Serine-Threonine Kinases, Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6, Tetradecanoylphorbol Acetate, Tissue Distribution, Transfection, Two-Hybrid System Techniques, Zinc Fingers
J. Biol. Chem.
Date: Aug. 10, 2001
PubMed ID: 11390377
View in: Pubmed Google Scholar
Download Curated Data For This Publication
8054
Switch View:
- Interactions 1