| Mechanism of inactivation of p53 |
Tumours |
Effect of inactivation |
| Amino acid mutation in the DNA binding domain |
Colon, breast, lung, bladder, brain, pancreas, stomach and esophagus |
Prevents p53 from binding to specific DNA sequences and activating the adjacent genes |
| Deletion of carboxyl terminal domain |
Occasional tumours at many other sites |
Prevents the formation of tetramers of p53 |
| Multiplication of Mdm2 gene in the genome |
Sarcomas and Brain tumours |
Extra Mdm2 stimulates the degradation of p53 |
| Viral infection |
Cervix, Liver and Lymphomas |
Products of viral oncogenes bind to and inactivate p53 in cell, in some cases stimulate p53 degradation |
| Deletion of p14 gene |
Breast, brain, lung and others (especially when p53 is not mutated) |
Failure to inhibit Mdm2 and maintains p53 degradation under control |
| Mislocalization of p53 to the cytoplasm, outside the nucleus |
Neuroblastomas, Breast carcinoma |
Lack of p53 function (p53 functions only in the nucleus) |
