Work

The Dual Specificity Phosphatase Cdc25C is a Direct Target for Transcriptional Repression by the Tumor Suppressor p53

Year: 2006

Type: review

Abstract: 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.

Source: Cell Cycle

DOI: 10.4161/cc.5.7.2628

Authors: Selvon St. Clair, James J. Manfredi

Institution: Icahn School of Medicine at Mount Sinai

Language: English

Topic: Cancer-related Molecular Pathways

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: U.S. Department of Defense, National Cancer Institute