p53 and Cell Cycle Dependent Transcription of kinesin family member 23 (KIF23) Is Controlled Via a CHR Promoter Element Bound by DREAM and MMB Complexes
Open Access
- 1 May 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (5), e63187
- https://doi.org/10.1371/journal.pone.0063187
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.Keywords
This publication has 65 references indexed in Scilit:
- Mechanisms of p53-mediated repression of the human polycystic kidney disease-1 promoterBiochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2010
- Clustering of Centralspindlin Is Essential for Its Accumulation to the Central Spindle and the MidbodyCurrent Biology, 2009
- Cell cycle, CDKs and cancer: a changing paradigmNature Reviews Cancer, 2009
- p53, cyclin-dependent kinase and abnormal amplification of centrosomesBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2008
- Cooperative Assembly of CYK-4/MgcRacGAP and ZEN-4/MKLP1 to Form the Centralspindlin ComplexMolecular Biology of the Cell, 2007
- α-Actinin Is Required for Tightly Regulated Remodeling of the Actin Cortical Network during CytokinesisDevelopmental Cell, 2007
- p21 delays tumor onset by preservation of chromosomal stabilityProceedings of the National Academy of Sciences of the United States of America, 2006
- The human synMuv-like protein LIN-9 is required for transcription of G2/M genes and for entry into mitosisThe EMBO Journal, 2006
- Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4α (HNF4α) geneBiochemical Journal, 2006
- Native E2F/RBF Complexes Contain Myb-Interacting Proteins and Repress Transcription of Developmentally Controlled E2F Target GenesCell, 2004