TUMOR PROTEIN

Tumor  protein  p53,  also  known  as  “the Guardian of the Genome”  because  of  its  role  in  conserving  stability  of   an  organism  by  preventing  genome  mutation. P53 plays a role in regulation or progression through the cell cycle, apoptosis, and genomic stability by means of several mechanisms. It can activate DNA repair proteins when DNA has damage. It can arrest growth by holding the cell cycle at the G1/S regulation point. It can initiate apoptosis (i.e., programmed cell death) if DNA damage proves to be irreparable.

 The name p53 was given in 1979 describing the apparent molecular mass; SDS-PAGE analysis indicates that it is a 53-kilodalton (kDa) protein. It is encoded by TP53 gene. In humans, the TP53 gene is located on the short arm of chromosome 17 (17p13.1).

In unstressed cells, p53 levels are kept low through a continuous degradation of p53. A protein called Mdm2 binds to p53. Mdm2 also acts as an ubiquitin ligase and covalently attaches ubiquitin to p53 and thus marks p53 for degradation by the proteasome. Phosphorylation of the N-terminal end of p53 by protein kinases disrupts Mdm2-binding. Other proteins, such as Pin1, are then recruited to p53 and induce a conformational change in p53, which prevents Mdm2-binding even more.

If the TP53 gene is damaged, tumor suppression is severely compromised. People who inherit only one functional copy of the TP53 gene will most likely develop tumors in early adulthood, a disorder known as Li-Fraumeni syndrome. The TP53 gene can also be modified by mutagens. Certain pathogens can also affect the p53 protein. One such example, human papillomavirus (HPV), encodes a protein, E6, which binds to the p53 protein and inactivates it.

More than 50 percent of human tumors contain a mutation or deletion of the TP53 gene. Loss of p53 creates genomic instability that most often results in an aneuploidy phenotype. In humans, a common polymorphism involves the substitution of an arginine for a proline at codon position 72. Many studies have investigated a genetic link between this variation and cancer susceptibility; however, the results have been controversial.

Regards,

Editorial Assistant,

Journal of Clinical Genomics

genomics@molecularbiol.com