DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: One involves direct binding to the cdc25C promoter

Selvon St Clair, Luciana Giono, Shohreh Varmeh-Ziaie, Lois Resnick-Silverman, Wen Jun Liu, Abhilash Padi, Jayasri Dastidar, Andrea DaCosta, Melissa Mattia, James J. Manfredi

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

The Cdc25C phosphatase mediates cellular entry into mitosis. The cdc25C gene is a target for transcriptional downregulation by the tumor suppressor protein p53, and this repression can be shown to contribute to p53-dependent cell cycle arrest. Two independent mechanisms have been identified. One involves the direct binding of p53 to a site in the cdc25C promoter, and the second involves a CDE/CHR element. Both of these mediate p53-dependent repression at levels of p53 comparable to those produced by DNA damage. Three CCAAT elements in the cdc25C promoter that were previously implicated in p53-dependent repression fail to do so at physiologically relevant levels of p53. Repression of Cdc25C by p53 represents an additional mechanism for p53-dependent cell cycle arrest in response to DNA damage. Importantly, this is a clear demonstration of p53-mediated transcriptional downregulation that is dependent on sequence-specific DNA binding by p53.

Original languageEnglish
Pages (from-to)725-736
Number of pages12
JournalMolecular Cell
Volume16
Issue number5
DOIs
StatePublished - 3 Dec 2004

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