IRF-1 induced cell growth inhibition and interferon induction requires the activity of the protein kinase PKR.
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.
Kirchhoff
S
S
GBF--Gesellschaft für Biotechnologische Forschung mbH, Braunschweig, Germany.
Koromilas
A E
AE
Schaper
F
F
Grashoff
M
M
Sonenberg
N
N
Hauser
H
H
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006131:Growth Inhibitors; D066298:In Vitro Techniques; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D010750:Phosphoproteins / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D019892:eIF-2 Kinase
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase