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TRAF family proteins link PKR with NF-kappa B activation

Jesús Gil1, Maria Angel García, Paulino Gomez-Puertas

  • 1Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Campus Universidad Autónoma, 28049 Madrid, Spain.

Molecular and Cellular Biology
|May 4, 2004
PubMed

Insights

The double-stranded RNA (dsRNA)-dependent protein kinase PKR interacts with TRAF proteins to activate NF-kappa B. This interaction is crucial for PKR-mediated NF-kappa B activation, highlighting TRAF proteins as key downstream mediators.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) activates NF-kappa B through the I kappa B kinase (IKK) complex.
  • The precise molecular mechanisms and additional interacting partners in the PKR-mediated NF-kappa B activation pathway remain incompletely understood.

Purpose of the Study:

  • To investigate potential interactions between PKR and TNF receptor-associated factor (TRAF) proteins.
  • To elucidate the role of TRAF proteins in PKR-mediated NF-kappa B activation.

Main Methods:

  • Bioinformatic analysis of PKR sequence for TRAF-interacting motifs.
  • In vivo co-localization and physical interaction studies using immunoprecipitation and confocal microscopy.
  • Functional assays assessing NF-kappa B activity in TRAF-deficient cells and with dominant-negative TRAF molecules.

Main Results:

  • PKR possesses putative TRAF-interacting motifs, supported by computer modeling.
  • PKR physically interacts and co-localizes with TRAF family proteins in vivo, an interaction dependent on PKR dimerization.
  • PKR-mediated NF-kappa B activation is abrogated in cells lacking TRAF2 and TRAF5 or expressing dominant-negative TRAF variants.
  • A model for TRAF-PKR interaction was proposed, involving the TRAF C-terminal domain and a motif in the PKR kinase domain.

Conclusions:

  • TRAF family proteins are essential downstream mediators of PKR.
  • TRAF proteins play a critical role in the activation of NF-kappa B by PKR.
  • This study identifies a novel interaction and signaling pathway involving PKR and TRAF proteins.

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