The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6

FEBS Lett. 1999 Jan 15;442(2-3):147-50. doi: 10.1016/s0014-5793(98)01645-7.

Abstract

The zinc finger protein A20 is encoded by an immediate early response gene whose expression is induced by different inflammatory stimuli, including interleukin-1 (IL-1). Gene induction by IL-1 is mediated by activation of the transcription factor NF-kappaB, and requires the signal adapter protein TRAF6. The latter interacts with the NF-kappaB-inducing kinase NIK, which is believed to be part of the IkappaB kinase complex. Expression of A20 potently inhibits IL-1-induced NF-kappaB activation by an unknown mechanism. Inhibition of IL-1-induced NF-kappaB activation was found to be mediated by the C-terminal zinc finger-containing domain of A20. More importantly, we present evidence that A20 interferes with IL-1-induced NF-kappaB activation at the level of TRAF6, upstream of NIK. Moreover, A20 was shown to directly interact with TRAF6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line
  • DNA-Binding Proteins
  • Gene Expression Regulation* / drug effects
  • Humans
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Kidney / cytology
  • NF-kappa B / metabolism*
  • NF-kappaB-Inducing Kinase
  • Nuclear Proteins
  • Precipitin Tests
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteins / pharmacology
  • Sequence Deletion / genetics
  • Signal Transduction / drug effects
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 6
  • Transcriptional Activation
  • Transfection
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tumor Necrosis Factor-alpha / pharmacology
  • Zinc Fingers / physiology*

Substances

  • DNA-Binding Proteins
  • Interleukin-1
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Proteins
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 6
  • Tumor Necrosis Factor-alpha
  • Protein Serine-Threonine Kinases
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3