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)
Table 2: Many ways in which p53 malfunctions in human cancers [51].