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