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Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding partner for the p70S6 serine/threonine

Diana S Fleckenstein1, Wilhelm G Dirks, Hans G Drexler

  • 1Department of Human and Animal Cell Cultures, DSMZ-German Collection of Microorganisms and Cell Cultures, Mascheroder Weg 1B, 38124 Braunschweig, Germany.

Leukemia Research
|June 13, 2003
PubMed
Abstract

Insights

Tumor necrosis factor receptor-associated factor 4 (TRAF4) binds to p70S6K kinase, mediating TNF-induced signaling and activating p70S6K. TRAF4 also inhibits Fas-induced apoptosis, promoting cell survival.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • p70S6K is a key kinase regulating cell cycle and gene transcription.
  • p70S6K localizes to both cytosol and nucleus, suggesting diverse cellular roles.
  • The interaction partners and full functional role of p70S6K remain incompletely understood.

Purpose of the Study:

  • To identify novel binding partners of p70S6K.
  • To elucidate the role of TRAF4 in TNF-induced signaling pathways.
  • To investigate the potential anti-apoptotic function of TRAF4.

Main Methods:

  • Yeast two-hybrid screening to identify p70S6K interacting proteins.
  • Immunoprecipitation to confirm protein complex formation.
  • Transfection studies to assess TRAF4's role in signaling and apoptosis.

Main Results:

  • TRAF4 was identified as a novel binding partner of p70S6K.
  • TNF receptor stimulation induced the formation of TRAF4/p70S6K complexes.
  • TRAF4 expression was necessary for TNF-induced p70S6K activation and S6 phosphorylation.
  • TRAF4 expression inhibited Fas-induced apoptosis in HEK-293 cells.

Conclusions:

  • TNF receptor activation leads to p70S6K activation.
  • TRAF4 acts as a mediator in the TNF-induced signaling pathway.
  • TRAF4 possesses an anti-apoptotic function, inhibiting Fas-induced cell death.

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