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TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40

M Rothe1, V Sarma, V M Dixit

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

Science (New York, N.Y.)
|September 8, 1995
PubMed

Insights

Tumor necrosis factor receptor-associated factor 2 (TRAF2) mediates signaling for TNF-R2 and CD40 pathways. TRAF2 overexpression activates NF-kappa B, while a TRAF2 derivative inhibits this activation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Tumor necrosis factor (TNF) receptor superfamily members signal through associated proteins.
  • TNF receptor-associated factor (TRAF) proteins are key signal transducers.
  • TRAFs link TNF receptors to downstream signaling pathways, including NF-kappa B activation.

Purpose of the Study:

  • To investigate the role of TRAF proteins in TNF-R2 and CD40 signal transduction.
  • To determine which TRAF proteins mediate NF-kappa B activation via these receptors.

Main Methods:

  • Overexpression of TRAF1, TRAF2, and TRAF3.
  • Utilizing a dominant-negative TRAF2 mutant lacking the RING finger domain.
  • Assessing NF-kappa B activation in response to TNF-R2 and CD40 stimulation.

Main Results:

  • TRAF2 overexpression alone induced NF-kappa B activation.
  • TRAF1 and TRAF3 overexpression did not activate NF-kappa B.
  • A truncated TRAF2 inhibited NF-kappa B activation mediated by both TNF-R2 and CD40.

Conclusions:

  • TRAF2 is a crucial and common mediator in TNF-R2 and CD40 signaling pathways.
  • The RING finger domain of TRAF2 is essential for its signaling function.
  • TRAF2 plays a central role in transmitting signals from TNF-R2 and CD40 to activate NF-kappa B.

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