Identification of a novel class of genomic DNA-binding sites suggests a mechanism for selectivity in target gene activation by the tumor suppressor protein p53.
There are two response elements for p53 in the promoter of the gene for the cyclin-dependent kinase inhibitor p21. The binding of p53 to the 5' site was enhanced by incubation with monoclonal antibody 421, whereas the binding of p53 to the 3' site was inhibited. Mutational analysis showed that a single-base change caused one element to behave like the other. A response element in the human cdc25C promoter is bound by p53 with properties similar to the 3' site. These results identify two classes of p53-binding sites and suggest a mechanism for target gene selectivity by p53.
Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029 USA.
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Resnick-Silverman
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St Clair
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Maurer
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Zhao
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Manfredi
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D018411:Spodoptera; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D020687:cdc25 Phosphatases
D000911:Antibodies, Monoclonal; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D004247:DNA; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases