Gene expression of cyclin-dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 but not by the related proteins p63 or p73.
Cks2 proteins are essential components of cyclin/cyclin-dependent kinase complexes and contribute to cell cycle control. We identify Cks2 as a transcriptional target downregulated by the tumor suppressor p53. Cks2 expression was found to be repressed by p53 both at the mRNA and the protein levels. p53 downregulates transcription from the Cks2 promoter in a dose-dependent manner and in all cell types tested. This repression appears to be independent of p53 binding to the Cks2 promoter. In contrast to p53, neither p63 nor p73 proteins can repress Cks2 transcription. Thus p53, rather than its homologues p63 and p73, may contribute to control of the first metaphase/anaphase transition of mammalian meiosis by downregulation of Cks2 expression.
Rother
Karen
K
Medizinische Klinik II, Max-Bürger-Forschungszentrum, Universität Leipzig, Johannisallee 30, D-04103 Leipzig, Germany.
Dengl
Markus
M
Lorenz
Jana
J
Tschöp
Katrin
K
Kirschner
Ralf
R
Mössner
Joachim
J
Engeland
Kurt
K
D000705:Anaphase; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D008540:Meiosis; D008565:Membrane Proteins / Q000502:physiology*; D008677:Metaphase; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
C081876:CKAP4 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D042846:CDC2-CDC28 Kinases; C083689:CKS2 protein, human