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lüll The dual specificity phosphatase Cdc25C is a direct target for transcriptional repression by the tumor suppressor p53 St Clair S; Manfredi JJCell Cycle 2006[Apr]; 5 (7): 709-13The 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.|Animals[MESH]|Cell Cycle Proteins/*genetics/*metabolism[MESH]|Humans[MESH]|Models, Genetic[MESH]|Promoter Regions, Genetic/genetics[MESH]|Repressor Proteins/*metabolism[MESH]|Transcription, Genetic/*genetics[MESH]|Tumor Suppressor Protein p53/*metabolism[MESH]|cdc25 Phosphatases/*genetics/*metabolism[MESH] |