p53 and breast cancer

The p53 gene, located at 17p13.3, was long thought to produce only one protein, but it has recently been discovered that, via alternative splicing and an internal promoter, the gene can in fact make up to nine different protein isoforms.3,4 The main protein product of the p53 gene is a phosphoprotein comprising 393 amino acid residues (Figure 12.2), with at least four recognized, highly conserved “boxes” or “domains”: the N-terminal (amino-terminal) transactivation domain;2 central DNA-binding domain; a tetramerization domain; and the C-terminal negative regulatory domain. Although each domain is involved in distinct and independent functions, overall they are interdependent in the sense that alterations within one domain can profoundly influence the functions of the other domains.5 The biological relevance of the p53 isoforms is actively being investigated, and the expression of the different isoforms could determine cell fate in response to cellular stress4 and may be related to prognosis in breast cancer.