DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: one involves direct binding to the cdc25C promoter.
DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: one involves direct binding to the cdc25C promoter.
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DOI：
10.1016/j.molcel.2004.11.002
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发表时间：
2004-12
期刊：
影响因子：
16
通讯作者：
Selvon F. St. Clair;L. Giono;S. Varmeh-Ziaie;L. Resnick-Silverman;Wen-jun Liu;Abhilash Padi;Jayasri Dast
中科院分区：
文献类型：
--
作者：
Selvon F. St. Clair;L. Giono;S. Varmeh-Ziaie;L. Resnick-Silverman;Wen-jun Liu;Abhilash Padi;Jayasri Dast
The Cdc25C phosphatase mediates cellular entry into mitosis. Thecdc25Cgene 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 thecdc25Cpromoter, 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 thecdc25Cpromoter 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.
