Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage

Nature. 1996 Aug 29;382(6594):816-8. doi: 10.1038/382816a0.


Normally growing cells promptly cease DNA synthesis when exposed to genotoxic stresses, such as radiation, and this cell-cycle arrest prevents the accumulation of mutations. The transcription factor interferon regulatory factor (IRF)-1 is essential for the regulation of the interferon system, inhibits cell growth, and manifests tumour-suppressor activities. Here we show that mouse embryonic fibroblasts (EFs) lacking IRF-1 are deficient in their ability to undergo DNA-damage-induced cell-cycle arrest. A similar phenotype has been observed in EFs lacking the tumour suppressor p53 (refs 8, 9), although the expression of IRF-1 and p53 are independent of one another. Furthermore, we show that transcriptional induction of the gene encoding p21 (WAF1, CIP1), a cell-cycle inhibitor, by gamma-irradiation is dependent on both p53 and IRF-1, and that the p21 promoter is activated, either directly or indirectly, by both in a transient cotransfection assay. These two tumour-suppressor transcription factors therefore converge functionally to regulate the cell cycle through the activation of a common target gene.

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Cycle / radiation effects
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / genetics
  • DNA Damage*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gamma Rays
  • Gene Expression Regulation
  • Interferon Regulatory Factor-1
  • Mice
  • Mutation
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*


  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • Phosphoproteins
  • RNA, Messenger
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinases