Expression of cyclin-dependent kinase subunit 1 (Cks1) is regulated during the cell cycle by a CDE/CHR tandem element and is downregulated by p53 but not by p63 or p73.
Cks1 is a member of the cyclin-dependent kinase subunit family. These proteins are essential components of cyclin/cyclin-dependent kinase (cdk) complexes contributing to cell cycle control in all eukaryotes. Cks1 protein is found overexpressed in a number of tumors. Expression of Cks1 mRNA starts in late G1 reaching a peak in S/G2-phases of the cell cycle. We find that this expression pattern depends on transcriptional regulation and is controlled by a combination of a cell cycle-dependent element (CDE) together with a cell cycle genes homology region (CHR) in the Cks1 promoter. Furthermore, we observe Cks1 mRNA and protein to be downregulated after induced expression of the tumor suppressor p53. This repression is due to p53 downregulating transcription from the Cks1 promoter. p53-dependent repression is seen in a dose-dependent manner and in several cell types of different origin. In contrast to p53, its homologues p63 and p73 do not significantly repress transcription from the Cks1 promoter. The Cks1 promoter does not contain a p53 binding site. For some promoters the CCAAT box-binding transcription factor NF-Y had been implicated in p53-dependent repression. NF-Y is the main activator for Cks1 transcription but does not influence p53-dependent repression from the Cks1 promoter. Generally, the observation that the potential oncogene Cks1 is downregulated by the tumor suppressor p53 corresponds well with the idea that p53 employs multiple ways in order to halt the cell cycle.
Rother
Karen
K
Medizinische Klinik II, Max-Bürger-Forschungszentrum, Universität Leipzig, Leipzig, Germany.
Li
Yong-Yu
YY
Tschöp
Katrin
K
Kirschner
Ralf
R
Müller
Gerd A
GA
Mössner
Joachim
J
Engeland
Kurt
K
D000818:Animals; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020080:Tandem Repeat Sequences / Q000235:genetics; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D023081:CCAAT-Binding Factor; C081876:CKAP4 protein, human; C093090:CKS1B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D042846:CDC2-CDC28 Kinases; D018844:Cyclin-Dependent Kinases