The dual specificity phosphatase Cdc25C is a direct target for transcriptional repression by the tumor suppressor p53.
The cdc25C gene has been shown to be a novel target for transcriptional downregulation by p53. Two independent mechanisms contribute to the p53-dependent repression of the cdc25C gene. First, an element in the cdc25C promoter consisting of a binding site for p53 plus an adjacent 8 base pairs confers p53-dependent repression. Mutation of either the p53 binding site or the adjacent 8 bp sequence abolishes this effect. The element conferring p53-dependent repression also contains a binding site for the transcription factor Sp1 and a mutant p53 protein that retains the ability to interact with the p53-binding site is defective in mediating repression. Second, a minimal promoter lacking the p53 binding site but containing a previously characterized CDE/CHR element is also repressed by p53. This repression is abrogated when a 5 bp mutation is introduced in the CHR sequence. These results support a model for p53 downregulating cdc25C expression, in part, by direct binding to a promoter element that is likely to require cooperation with an additional cellular factor.
Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
Selvon
S
St Clair
James J
JJ
Manfredi
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000235:genetics* / Q000378:metabolism*
D018797:Cell Cycle Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases