PIASy represses TRIF-induced ISRE and NF-kappaB activation but not apoptosis

FEBS Lett. 2004 Jul 16;570(1-3):97-101. doi: 10.1016/j.febslet.2004.05.081.

Abstract

The TIR domain-containing adapter protein TRIP is critically involved in TLR3-induced IFN-beta production through activation of NF-kappaB and ISRE. In addition, TRIF also induces apoptosis when overexpressed in 293 cells. In this report, we demonstrate that PIASy, a member of the PIAS SUMO-ligase family, interacts with TRIP, IRF-3 and IRF-7. In reporter gene assays, PIASy dramatically inhibits TRIF-induced NF-kappaB, ISRE and IFN-beta activation but not TRIF-induced apoptosis. Furthermore, PIASy also inhibits IRF-3, IRF-7 and Sendai virus-induced ISRE activation. Our results suggest that PIASy is an inhibitor of TRIF-induced ISRE and NF-kappaB activation but not apoptosis.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Apoptosis*
  • Blotting, Western
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Genes, Dominant
  • Genes, Reporter
  • Humans
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon-beta / metabolism
  • Interferons / metabolism*
  • Intracellular Signaling Peptides and Proteins*
  • Luciferases / metabolism
  • Mutation
  • NF-kappa B / metabolism*
  • Poly-ADP-Ribose Binding Proteins
  • Precipitin Tests
  • Protein Binding
  • Protein Inhibitors of Activated STAT
  • Protein Structure, Tertiary
  • Receptors, Tumor Necrosis Factor / metabolism
  • Response Elements
  • Sendai virus / metabolism
  • Transcription Factors / metabolism*
  • Transfection
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins

Substances

  • Adaptor Proteins, Vesicular Transport
  • Carrier Proteins
  • DNA-Binding Proteins
  • IRF3 protein, human
  • IRF7 protein, human
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • PIAS4 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Protein Inhibitors of Activated STAT
  • Receptors, Tumor Necrosis Factor
  • TICAM-1 protein, mouse
  • TICAM1 protein, human
  • Transcription Factors
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Interferon-beta
  • Interferons
  • Luciferases