P53 AND CANCERS

The p53 gene, located on chromosome 17p 13.1 and coding for a nuclear 393 amino-acids phosphoprotein acts to constrain or antagonize cell gr owth, and as such, is a tumor suppressor gene. In fact, inactivation o f p53 tumor suppressor gene is a common event in the development of al l or most types of human cancers. About half of cell cancer cases anal ysed thus far involve missense mutation of one p53 allele combined wit h the deletion of the second allele, and many of the remaining cases i nvolve a functional inactivation of p53 protein through non mutational mechanisms. The importance of p53 as an inherited cancer susceptibili ty gene has been demonstrated in Li-Fraumeni syndrome. In some circums tances, it has been shown that in response to DNA damage, the p53 leve l in the cell increases considerably and induces a cell growth arrest late in G1 phase. This cycle arrest allows the altered DNA to be repai red before entry of the cell into S phase. This function of p53 helps to insure the genomic stability of the cell. Mutations in p53 eliminat e this response and result in enhanced frequency of genomic rearrangem ents. In other circumstances wild type p53 may act by triggering cell death by apoptosis. The p53 protein exerts its physiological functions through various biochemical activities. These include its ability to be a site-specific transcriptional transactivator as well as a repress or of transcription. The oncoproteins derived from several oncogenicDN A viruses including SV40 large T antigen, the adenovirus E1B protein, and papillomavirus E6 protein, as well as specific cellular gene produ cts e.g. mdm2 form complexes with the p53 protein, causing its inactiv ation. The current data on the role of p53 in tumorigenesis as well as some future developments in the field are discussed in this review.