IRF-1 induced cell growth inhibition and interferon induction requires the activity of the protein kinase PKR

Oncogene. 1995 Aug 3;11(3):439-45.

Abstract

Expression of the tumor suppressor IRF-1 results in the inhibition of cell growth and transcriptional activation of the IFN-beta gene. IFN production is not responsible for the IRF-1 mediated cell growth inhibition. It is shown here that activation of the IRF-1 causes induction of PKR expression. PKR is a serine/threonine kinase with tumor suppressor activity. IRF-1 mediated cell growth inhibition and IFN induction correlates with PKR expression. A catalytically inactive dominant negative PKR mutant abolishes both activities of IRF-1. These data demonstrate that the tumor suppressor activity of IRF-1 is mediated, at least in part, by PKR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Division / drug effects
  • DNA-Binding Proteins / pharmacology*
  • Gene Expression / drug effects
  • Genes, Tumor Suppressor
  • Growth Inhibitors
  • In Vitro Techniques
  • Interferon Regulatory Factor-1
  • Interferons / biosynthesis*
  • Interferons / genetics
  • Mice
  • Phosphoproteins / pharmacology*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / genetics
  • eIF-2 Kinase

Substances

  • DNA-Binding Proteins
  • Growth Inhibitors
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • Phosphoproteins
  • RNA, Messenger
  • Interferons
  • Protein Serine-Threonine Kinases
  • eIF-2 Kinase