Expression of the cell cycle phosphatase cdc25C is down-regulated by the tumor suppressor protein p53 but not by p73.
The cdc25C phosphatase dephosphorylates cdc2 kinase which then in complex with cyclin B can catalyse transition from the G(2) phase to mitosis. We demonstrate that transcription of cdc25C is repressed by p53 in a dose-dependent manner. In stably transfected DLD-1 colorectal adenocarcinoma cells, cdc25C expression is down-regulated when p53 is induced from a (tet)-off-regulated system. In contrast to p53, its homologue p73 is not able to down-modulate cdc25C expression. A previously identified site in the cdc25C promoter can bind p53 in vitro and, when placed in a heterologous construct, is able to activate transcription. However, transcriptional repression by p53 is not mediated through this site but is dependent on a segment containing three CCAAT-boxes. In general down-regulation of cdc25C transcription by reducing the levels of active cdc2 kinase contributes to G(2) arrest and G(2)/M checkpoint control. This reveals functional differences between p73 and p53 in regulating cell division.
Krause
K
K
Department of Internal Medicine II, University of Leipzig, Max Bürger Research Centre, Johannisallee 30, D-04103 Leipzig, Germany.
Haugwitz
U
U
Wasner
M
M
Wiedmann
M
M
Mössner
J
J
Engeland
K
K
D000818:Animals; D023081:CCAAT-Binding Factor / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020218:Response Elements; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D020687:cdc25 Phosphatases / Q000096:biosynthesis / Q000235:genetics*
D023081:CCAAT-Binding Factor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D020687:cdc25 Phosphatases