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Updated: Aug 9, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB

H Y Song1, M Rothe, D V Goeddel

  • 1Tularik, Inc., South San Francisco, CA 94080, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 25, 1996
PubMed

Insights

Tumor necrosis factor receptor-associated factor 1 (TRAF1) and TRAF2 interact with the protein A20. A20 inhibits NF-kappaB activation, suggesting a negative feedback mechanism in TNF signaling.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • TRAF1 and TRAF2 are crucial for TNF receptor superfamily signaling and NF-kappaB activation.
  • NF-kappaB is a transcription factor activated by various stimuli, including TNF and CD40 ligand.
  • A20 is a zinc finger protein induced by NF-kappaB activating agents.

Purpose of the Study:

  • To investigate the interaction between A20, TRAF1, and TRAF2.
  • To elucidate the mechanism by which A20 regulates NF-kappaB activation.
  • To understand A20's role in negative feedback of TNF-inducible gene expression.

Main Methods:

  • Co-transfection experiments to study protein interactions and functional effects.
  • Mutational analysis to map functional domains of A20.
  • Assays to measure NF-kappaB activation.

Main Results:

  • A20 directly interacts with TRAF1 and TRAF2 via its N-terminal domain.
  • A20 inhibits TRAF2-mediated NF-kappaB activation.
  • A20's C-terminal zinc finger domain mediates the inhibition of NF-kappaB activation.
  • A20 inhibits NF-kappaB activation induced by TNF and IL-1.

Conclusions:

  • A20 functions as a negative regulator of NF-kappaB signaling.
  • A20 possesses distinct functional domains: one for TRAF binding and another for NF-kappaB inhibition.
  • A20 may provide a molecular mechanism for negative feedback regulation of its own expression in response to TNF signaling.

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