Abstract
The microtubule-dependent molecular motor KIF23 (Kinesin family member 23) is one of two components of the centralspindlin complex assembled during late stages of mitosis. Formation of this complex is known as an essential step for cytokinesis. Here, we identified KIF23 as a new transcriptional target gene of the tumor suppressor protein p53. We showed that p53 reduces expression of KIF23 on the mRNA as well as the protein level in different cell types. Promoter reporter assays revealed that this repression results from downregulation of KIF23 promoter activity. CDK inhibitor p21(WAF1/CIP1) was shown to be necessary to mediate p53-dependent repression. Furthermore, we identified the highly conserved cell cycle genes homology region (CHR) in the KIF23 promoter to be strictly required for p53-dependent repression as well as for cell cycle-dependent expression of KIF23. Cell cycle- and p53-dependent regulation of KIF23 appeared to be controlled by differential binding of DREAM and MMB complexes to the CHR element. With this study, we describe a new mechanism for transcriptional regulation of KIF23. Considering the strongly supporting function of KIF23 in cytokinesis, its p53-dependent repression may contribute to the prevention of uncontrolled cell growth.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Cycle
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Gene Expression Regulation
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Gene Silencing*
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HCT116 Cells
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Humans
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Kv Channel-Interacting Proteins / metabolism*
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Mice
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Microtubule-Associated Proteins / genetics*
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Microtubule-Associated Proteins / metabolism
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NIH 3T3 Cells
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Oncogene Proteins v-myb / metabolism*
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Promoter Regions, Genetic*
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Protein Binding
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Stability
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Repressor Proteins / metabolism*
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Response Elements
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Transcription, Genetic
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Tumor Suppressor Protein p53 / metabolism*
Substances
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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KCNIP3 protein, human
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KIF23 protein, human
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Kv Channel-Interacting Proteins
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Microtubule-Associated Proteins
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Oncogene Proteins v-myb
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Protein Isoforms
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RNA, Messenger
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Repressor Proteins
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TP53 protein, human
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Tumor Suppressor Protein p53
Grants and funding
MQ is recipient of graduate fellowship awarded by the Freistaat Sachsen, SS was supported by a junior research grant and IG was the recipient of thesis support grant awarded by the Medical School at the University of Leipzig. This work was supported by grants from the Fonds der Chemische Industrie and the Forschungsausschuss of the Saarland University (to KR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.