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
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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. / Fischer, Martin; Grundke, Inga; Sohr, Sindy; Quaas, Marianne; Hoffmann, Saskia; Knörck, Arne; Gumhold, Catalina; Rother, Karen.
In: PLoS ONE, Vol. 8, No. 5, 2013, p. e63187.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Fischer, Martin
AU - Grundke, Inga
AU - Sohr, Sindy
AU - Quaas, Marianne
AU - Hoffmann, Saskia
AU - Knörck, Arne
AU - Gumhold, Catalina
AU - Rother, Karen
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Cycle
KW - Cyclin-Dependent Kinase Inhibitor p21/metabolism
KW - Gene Expression Regulation
KW - Gene Silencing
KW - HCT116 Cells
KW - Humans
KW - Kv Channel-Interacting Proteins/metabolism
KW - Mice
KW - Microtubule-Associated Proteins/genetics
KW - NIH 3T3 Cells
KW - Oncogene Proteins v-myb/metabolism
KW - Promoter Regions, Genetic
KW - Protein Binding
KW - Protein Isoforms/genetics
KW - Protein Stability
KW - RNA, Messenger/genetics
KW - Repressor Proteins/metabolism
KW - Response Elements
KW - Transcription, Genetic
KW - Tumor Suppressor Protein p53/metabolism
U2 - 10.1371/journal.pone.0063187
DO - 10.1371/journal.pone.0063187
M3 - Journal article
C2 - 23650552
VL - 8
SP - e63187
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 5
ER -
ID: 237849703