Nucleic Acids Research, 1992, Vol. 20, No. 15 4083-4087
© 1992
MOLECULAR BIOLOGY |
Repression of the basal c-fos promoter by wild-type p53
Molecular Neuro-Oncology Laboratory, Neuroscience Center, Massachusetts General Hospital and Harvard Medical School Charlestown, MA 02129, USA 1Laboratorie de Physiologie Generale, URA 309 du CNRS, Universiteè Louis Pasteur Strasbourg Cedex, France
Received February 28, 1992. Accepted June 7, 1992.
Mutations In the p53 gene are the most common genetic alterations observed in many inherited and sporadic forms of human cancer. Recent studies indicate that wild-type p53 may be involved in the regulation of gene expression. In the present report we examined the effect of p53 on the human c-fos promoter. Using a transient co-transfection assay we show that wild-type human p53, but not a transforming mutant of p53, negatively regulates the activity of the c-fos promoter in a dose-dependent manner. Promoter deletion analysis maps a sequence confering p53 repression to the basal promoter region between nucleotides - 53 and + 42 relative to the cap site. In contrast, p53 strongly stimulates transcription when a sequence previously reported to bind p53 (TGCCT repeat) was inserted In front of the HSV-TK promoter driving CAT. These findings raise the question as to whether p53 may mediate its inhibitory effect on c-fos gene expression by interfering, directly or indirectly, with components of the basal transcriptional machinery.
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