Moreover,oncogenic forms of p53 inhibit the ability of wildtype p53 to stimulate reporter genes. Human tumors frequently express large amounts of p53 antigen. These and other results suggest that, although p53 null mutations are oncogenic, oncogenicity is most frequently due to dominant negative mutations that result in production of a defective p53 that oligomerizes and interferes with the function of wildtype p53. Yeast studies have helped our understanding of the role of p53 in preventing human cancer in many ways. It is becoming increasingly clear that cancer results from a problem in cell cycle control.
All humans probably have somatic cell mutations in tumor suppressor genes.
These mutations do not cause cancer because higher eukaryotic organisms, being diploid, have a nonmutated copy of the gene to provide functional copies of the protein. As long as the cell faithfully replicates its chromosomes during S phase and segregates its chromosomes during M phase, the heterozygous condition persists and the cell remains normal. Although yeast does not contain a p53 gene, the similarity of cell cycle control mechanisms and transcriptional mechanisms in all eukaryotic organisms has prompted investigators to ask whether human p53 is active in yeast and whether its activity is affected by yeast mutations. A very recent study, done with the fission yeast S. pombe , found that high level expression of p53 in S. pombe arrested cell growth. A mutant circumventing the growth arrest of p53 was isolated and the gene was cloned.