p53 (TP53) is a tumour suppressor gene, sometimes dubbed the 'guardian of the genome'. First described in 1979, the expressed protein is thought to exert its function by monitoring the integrity of the genome and preventing the passage of DNA damage through co-ordinating several mechanisms, e.g. inducing apoptosis, inducing cell cycle arrest or facilitating DNA repair by delaying the cell cycle.
Mutations in the p53 tumour suppressor gene are found in over 50% of human tumours, including 60% of lung cancers.. A rare, autosomally dominant syndrome, called Li-Fraumeni syndrome results in early onset of several types of cancers.
A theory of cancer genesis is of accumulation of damage, sequentially, to several intracellular control systems each of which would prevent the initial cell running wild, which might still be headed off by an immune system reaction, but in a proportion of instances is not, leading to propagation of the clone of tumour cells. The myriad pathways of oncogenesis thus pass through a number of common gateways.
The p53 system is one of the more ancient, fundamental and powerful of these stop-systems and if it is knocked out uncontrolled cell division becomes likely.
- ↑ Lane DP. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2; 358(6381):15-6.(Link to article – subscription may be required.)
- ↑ Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15; 278(5701):261-3.
- ↑ Bitton A, Neuman MD, Barnoya J, Glantz SA. The p53 tumour suppressor gene and the tobacco industry: research, debate, and conflict of interest. Lancet. 2005 Feb 5-11; 365(9458):531-40.(Link to article – subscription may be required.)