The c-fos Proto-Oncogene Is a Target for Transactivation by the p53 Tumor Suppressor
AUTOR(ES)
Elkeles, Adi
FONTE
American Society for Microbiology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84052Documentos Relacionados
- c-fos proto-oncogene expression in the nervous system during mouse development.
- Chromatin association and DNA binding properties of the c-fos proto-oncogene product.
- Antisense RNA of proto-oncogene c-fos blocks renewed growth of quiescent 3T3 cells.
- The heat shock response in HeLa cells is accompanied by elevated expression of the c-fos proto-oncogene.
- Degradation of the proto-oncogene product c-Fos by the ubiquitin proteolytic system in vivo and in vitro: identification and characterization of the conjugating enzymes.
