The tumor suppressor p53 regulates its own transcription.
The ability of p53 to suppress transformation correlates with its ability to activate transcription. To identify targets of p53 transactivation, we examined the p53 promoter itself. Northern (RNA) analysis and transient transfection experiments showed that p53 transcriptionally regulated itself. A functionally inactive mutant p53 could not regulate the p53 promoter. Deletion analysis of the p53 promoter delineated sequences between +22 and +67 as being critical for regulation. Electrophoretic mobility shift analysis and methylation interference pinpointed the p53 DNA responsive element. When oligomerized in front of a heterologous minimal promoter, this element was regulated by wild-type p53 and not by mutant p53. Point mutations in the DNA element that eliminated protein-DNA interactions also resulted in a nonresponsive p53 promoter. The DNA element in the p53 promoter responsive to p53 regulation is similar to the p53 consensus sequence. However, we have been unable to detect a direct interaction of p53 with its promoter.
Deffie
A
A
Department of Molecular Genetics, M.D. Anderson Cancer Center, University of Texas, Houston 77030.
Wu
H
H
Reinke
V
V
Lozano
G
G
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005786:Gene Expression Regulation; D016158:Genes, p53; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D017384:Sequence Deletion; D013724:Teratoma; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
D009838:Oligodeoxyribonucleotides; D016159:Tumor Suppressor Protein p53; D012313:RNA; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase