Reisman Lab Publications
Loging, W.T. and Reisman, D. 1999 Elevated Expression of Ribosomal Protein Genes L37, RPP-l, and S2 in the Presence of Mutant p53. Cancer, Epidemiology, Biomarkers, and Prevention 8,1011-6.
The wild type p53 protein is a DNA-binding transcription factor that activates genes such as p21, MDM2, GADD45 and Bax that are required for the regulation of cell cycle progression or apoptosis in response to DNA damage. Mutant forms of p53, which are transforming oncogenes and are expressed at high levels in tumor cells, generally have a reduced binding affinity for the consensus DNA sequence. Interestingly, some p53 mutants that no longer are effective at binding to the consensus DNA sequence and transactivating promoters containing this target site, have acquired the ability to transform cells in culture in part through their ability to transactivate promoters of a number of genes that are not targets of the wild type protein. Certain p53 mutants then are considered to be gain-of-function mutations and appear to be promoting proliferation or transforming cells through their ability to alter expression of novel sets of genes. Our goal is to identify genes that have altered expression in the presence of a specific mutant p53 protein. Through examining differential gene expression in cells devoid of p53 expression and ~n cells generated which express high levels of mutant p53 protein, we have identified three ribosomal protein genes that are elevated in their expression in response to mutant p53. Consistent with these findings, the overexpression of a number of ribosomal protein genes in human tumors and evidence for their contribution to oncogenic transformation has been previously reported, although the mechanism leading to this overexpression has remained elusive. We show results that indicate expression of these specific ribosomal protein genes are increased in the presence of the R24SW p53 mutant which provide a mechanism for their overexpression in human tumors.