Transactivation of the human p53 tumor suppressor gene by c-Myc/Max contributes to elevated mutant p53 expression in some tumors

Baishali Roy, John Beamon, E. Bálint, David Reisman

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Abstract

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 is due to deregulated 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. To determine whether the p53 gene can be a target for c-Myc in vivo, we assayed the effects of antisense c-myc RNA on the levels of endogenous p53 mRNA. The results indicate that the presence of antisense 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 support a direct role for c-Myc in elevating expression of the mutant p53 gene in some tumors.

Original languageEnglish
Pages (from-to)7805-7815
Number of pages11
JournalMolecular and Cellular Biology
Volume14
Issue number12
Publication statusPublished - Dec 1994

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Tumor Suppressor Genes
Transcriptional Activation
Proto-Oncogene Proteins c-myc
Messenger RNA
p53 Genes
Neoplasms
RNA
Burkitt Lymphoma
Protein Stability
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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Transactivation of the human p53 tumor suppressor gene by c-Myc/Max contributes to elevated mutant p53 expression in some tumors. / Roy, Baishali; Beamon, John; Bálint, E.; Reisman, David.

In: Molecular and Cellular Biology, Vol. 14, No. 12, 12.1994, p. 7805-7815.

Research output: Contribution to journalArticle

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