What happens if p53 is mutated?
Functional p53 integrates stress signals, including DNA damage, oncogene activation, and hypoxia, to decide between cell cycle arrest, senescence, or apoptosis. Under normal conditions, wild-type p53 accumulates after ATM phosphorylates serine 15 and CHK2 phosphorylates serine 20, displacing E3 ubiquitin ligase MDM2 that normally targets p53 for proteasomal degradation. Transcriptional program includes CDKN1A encoding p21 inhibitor of CDK2-cyclin E and CDK4-cyclin D, causing Rb to remain hypophosphorylated and E2F-dependent S-phase entry genes repressed, imposing G1 arrest to allow repair. If
Ref: Vogelstein et al., Nature 2000, Surfing p53 Network; Levine & Oren, Nature Rev Cancer 2009, p53 Mutations.