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

The p53 tumor suppressor gene is mutated in over 50% of human cancers, resu lting in inactivation of the wild-type (wt) p53 protein, The most notable b iochemical feature of p53 is its ability to act as a sequence-specific tran scriptional activator. Through use of the suppression subtractive hybridiza tion differential screening technique, we identified c-fos as a target for transcriptional stimulation by p53 in cells undergoing p53-mediated apoptos is. Overexpression of wt p53 induces c-fos mRNA and protein. Moreover, in v ivo induction of c-fos in the thymus following whole-body exposure to ioniz ing radiation is p53 dependent. p53 responsiveness does not reside in the b asal 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 ab ility 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 .