How p53 induces cell cycle arrest in DNA damaged cells?

p53 is a 53kd tumor suppressor protein that prevents cell cycle progression of cells with damaged DNA.
On DNA damage, p53 is phosphorylated, Activated p53 induces production of another protein p21 which is a CdK inhibitor.[(CdKs or cyclin dependent kinases are required for cell cycle progression from G1 to S phase (Cdk2) and G2 to M phase(Cdc2)]. Thus p53 induces G1-S and G2-M phase cell cycle arrest.

The progression into the M phase requires Cdc2 which can be inhibited by p21,  GADD45 etc which are all regulated by p53.

Cell cycle arrest by p53

Summary flow chart
DNA damage—> activates Kinase—> Phosphorylation of p53 by kinases—> P21 production induced by p53—> P21 inhibits Cdks activity—> lead to G1-S or G2-M arrest

  • 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).

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