Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Base Sequence
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Blotting, Northern
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Blotting, Western
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Carrier Proteins / biosynthesis*
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Cell Line
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Cloning, Molecular
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DNA, Complementary / metabolism
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DNA-Binding Proteins
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Humans
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I-kappa B Kinase
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Intracellular Signaling Peptides and Proteins
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Molecular Sequence Data
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Nuclear Proteins
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Plasmids / metabolism
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Precipitin Tests
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Protein Binding
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism
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Proteins / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Signal Transduction
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TNF Receptor-Associated Factor 2
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TNF Receptor-Associated Factor 6
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Tetradecanoylphorbol Acetate / pharmacology
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Tissue Distribution
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Transfection
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Tumor Necrosis Factor alpha-Induced Protein 3
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Two-Hybrid System Techniques
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Zinc Fingers
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DNA, Complementary
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DNA-Binding Proteins
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Enzyme Inhibitors
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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Nuclear Proteins
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Proteins
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TNF Receptor-Associated Factor 2
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TNF Receptor-Associated Factor 6
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TNIP2 protein, human
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Protein Serine-Threonine Kinases
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CHUK protein, human
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human
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TNFAIP3 protein, human
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Tumor Necrosis Factor alpha-Induced Protein 3
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Tetradecanoylphorbol Acetate
Associated data
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GENBANK/AJ304865
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GENBANK/AJ304866