P53 is a 53kd tumor suppressor protein that prevents cell cycle progression of cells with damaged DNA.
Apoptotic pathway is activated upon failure of DNA repair mechanisms to correct DNA damage. In this pathway, p53 on activation induces expression of BAX gene or Apaf-1 gene. The BAX gene product induces cell to undergo apoptosis or programmed cell death.
After more than 30 years of research in this gene, now it is very clear that p53 inactivation is essential for the onset of all types of cancers.
Apoptotic pathway is activated upon failure of DNA repair mechanisms to correct DNA damage. In this pathway, p53 on activation induces expression of BAX gene or Apaf-1 gene. The BAX gene product induces cell to undergo apoptosis or programmed cell death.
Summary flow chart
DNA damage —> activates Kinases-—> Phosphorylation of p53 by kinases—> failure of DNA damage repair àActivation of BAX gene by p53-—> Cytochrome C release from mitochondrion—> caspase -9 (executioner caspase) —> apoptosis
OR
DNA damage—> activates Kinases—> Phosphorylation of p53 by kinases—> failure of DNA damage repair —> activation of Apaf1 by p53—> Cytochrome C release from mitochondrion—> caspase -9—> Apaf1+Cytochrome C +caspase -9 complex —> apoptosis.
After more than 30 years of research in this gene, now it is very clear that p53 inactivation is essential for the onset of all types of cancers.
References:
- p53 : The Most Frequently Altered Gene in Human Cancers. Nature Education 3(9):6
- Momand, J., Zambetti, G. P., et al. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69,1237–1245 (1992).
- Haupt, Y., Maya, R., et al. Mdm2 promotes the rapid degradation of p53. Nature 387, 296–299 (1997).