p53 (TP53)
p53, encoded by the TP53 gene, is a transcription factor that collects stress signals from across the cell and commits the cell to one of several fates: cell-cycle arrest, DNA repair, senescence, or apoptosis.
Function
In a healthy cell, p53 is kept at low levels by rapid degradation. DNA damage, oncogene activation, hypoxia, and telomere shortening each interrupt this degradation, and p53 accumulates. The accumulated protein binds DNA and activates a program of target genes whose combined effect halts division until the damage is repaired, or — when the damage is beyond repair — removes the cell. MDM2 is the principal regulator of this switch, and p21 and 14ARF sit among its downstream and upstream partners.
In cancer
TP53 is the most frequently mutated gene in human cancer. Loss of p53 removes the cell’s damage checkpoint, so a cell that accumulates mutations keeps dividing instead of arresting or dying. The gene’s two-hit inheritance pattern follows the classic [tumor suppressor](Types of tumor suppressor genes.md) logic, and its stress-integrating role makes it a central node in cellular senescence, the DNA damage response, and the organism’s audit of its cell lineages.
Notes
- Human gene symbol: TP53; protein name: cellular tumor antigen p53; UniProt P04637; 393 amino acids.
- Discovered in 1979; recognized first as an oncogene, then recharacterized as a tumor suppressor in 1989.
- Mouse knockout phenotype: normal development, early tumor incidence.