The c-fos proto-oncogene is a target for transactivation by the p53 tumor suppressor

Mol Cell Biol. 1999 Apr;19(4):2594-600. doi: 10.1128/MCB.19.4.2594.


The p53 tumor suppressor gene is mutated in over 50% of human cancers, resulting in inactivation of the wild-type (wt) p53 protein. The most notable biochemical feature of p53 is its ability to act as a sequence-specific transcriptional activator. Through use of the suppression subtractive hybridization differential screening technique, we identified c-fos as a target for transcriptional stimulation by p53 in cells undergoing p53-mediated apoptosis. Overexpression of wt p53 induces c-fos mRNA and protein. Moreover, in vivo induction of c-fos in the thymus following whole-body exposure to ionizing radiation is p53 dependent. p53 responsiveness does not reside in the basal c-fos promoter. Rather, a distinct region within the c-fos gene first intron binds specifically to p53 and confers upon the c-fos promoter the ability to become transcriptionally activated by wt p53. Identification of c-fos as a specific target for transcriptional activation by p53 establishes a direct link between these two pivotal regulatory proteins and raises the possibility that c-fos contributes to some of the biological effects of p53.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • DNA Damage
  • Gene Expression Regulation
  • Introns
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-fos / genetics*
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / biosynthesis
  • Response Elements
  • Transcriptional Activation*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Suppressor Protein p53