Repression of the basal c-fos promoter by wild-type p53.
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 conferring 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.
Kley
N
N
Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Charlestown.
Chung
R Y
RY
Fay
S
S
Loeffler
J P
JP
Seizinger
B R
BR
D001483:Base Sequence; D015536:Down-Regulation / Q000235:genetics*; D016762:Genes, fos / Q000235:genetics*; D016158:Genes, p53; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D013937:Thymidine Kinase