Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2

J Biol Chem. 2001 Aug 10;276(32):30216-23. doi: 10.1074/jbc.M100048200. Epub 2001 Jun 4.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary / metabolism
  • DNA-Binding Proteins
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Humans
  • I-kappa B Kinase
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Nuclear Proteins
  • Plasmids / metabolism
  • Precipitin Tests
  • Protein Binding
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism
  • Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 6
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tissue Distribution
  • Transfection
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Two-Hybrid System Techniques
  • Zinc Fingers

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Proteins
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 6
  • TNIP2 protein, human
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tetradecanoylphorbol Acetate

Associated data

  • GENBANK/AJ304865
  • GENBANK/AJ304866