Reisman Lab Publications

Roy, B., Beamon, J., Balint, E. and Reisman. 1994. Transactivation of the human p53 tumor suppressor gene by c-Myc/Max contributes to elevated mutant p53 expression in some tumors. Mol. and Cell. Biol. 14, 7805-7815.

Elevated levels of mutant forms of the p53 tumor suppressor are a hallmark of many transformed cells. Multiple mechanisms such as increased stability of the protein and increased transcription of the gene can account for elevated p53 expression. Recent findings indicate that c-Myc/Max heterodimers can bind to an essential CA(C/T)GTG-containing site in the p53 promoter and elevate its expression. We have addressed the possibility that elevated mutant p53 expression may be due to de-regulated c-Myc expression. Here we demonstrate that the human p53 promoter is transactivated by high c-Myc expression and repressed by high Max expression. In examining the relative levels of c-Myc and p53 in human Burkitt's lymphomas and other B-lymphoid lines, we found that there is a correlation between the levels of c-Myc protein and p53 mRNA expression. In particular, cells that express very low levels of c-Myc protein also express low levels of p53 mRNA while cells that express high levels of c-Myc tend to express high levels of p53 mRNA. In order to ask whether the p53 gene can be a target for c-Myc in vivo we have assayed the effects of anti-sense c-myc RNA on the levels of endogenous p53 mRNA. The results indicate that the presence of anti-sense c-myc RNA leads to a reduction in the levels of c-Myc protein, p53 mRNA and expression from the p53 promoter. Taken together, our findings would support a direct role for c-Myc in elevating expression of the mutant p53 gene in some tumors.