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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

Karen Rother, Yong-Yu Li, Katrin Tschöp, Ralf Kirschner, Gerd A. Müller, Joachim Mössner and Kurt Engeland

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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.

Authors

Karen Rother

Universität Leipzig; Leipzig, Germany

Yong-Yu Li

Medical College of Tongji University, Shanghai, China

Katrin Tschöp

Universität Leipzig, Leipzig, Germany

Ralf Kirschner

Universität Leipzig, Leipzig, Germany

Gerd A. Müller

Universität Leipzig, Leipzig, Germany

Joachim Mössner

Universität Leipzig, Leipzig, Germany

Kurt Engeland

Universität Leipzig; Leipzig, Germany

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.