p53 Protein, biological and clinical aspects

Definition

p53 is a 53 kD protein a that was discovered in 1979 by virtue of its capacity to bind several viral antigens (SV40 large T antigen, E1B from adenovirus) or by its ability to induce a humoral response in tumor-bearing animals. Mouse and human p53 genes were cloned in 1983 and 1984, respectively. The p53 gene belongs to the category of tumor suppressor genes as it fulfils the three main criteria:

• homozygotic somatic alterations in human cancer

• germline mutations are associated with the Li-Fraumeni syndrome, a rare autosomal-dominant disease whose hallmark is a predisposition to a wide range of cancers among members of a family

• the p53 protein is a negative regulator of cell growth.

In addition, some mutant p53 can exert a dominant negative effect toward wild type p53. Furthermore, it is possible that several p53 mutants harbors a gain in function that suggests that mutant p53 could act as an oncogene.

Characteristics

The human p53 gene is localized on the short arm of...