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p53 can repress transcription of cell cycle genes through a p21WAF1/CIP1-dependent switch from MMB to DREAM protein complex binding at CHR promoter elements
- Source :
- Cell Cycle
- Publication Year :
- 2012
- Publisher :
- Informa UK Limited, 2012.
-
Abstract
- The tumor suppressor p53 plays an important role in cell cycle arrest by downregulating transcription. Many genes repressed by p53 code for proteins with functions in G₂/M. A large portion of these genes is controlled by cell cycle-dependent elements (CDE) and cell cycle genes homology regions (CHR) in their promoters. Cyclin B2 is an example of such a gene, with a function at the transition from G₂ to mitosis. We find that p53-dependent downregulation of cyclin B2 promoter activity is dependent on an intact CHR element. In the presence of high levels of p53 or p21(WAF1/CIP1), protein binding to the CHR switches from MMB to DREAM complex by shifting MuvB core-associated proteins from B-Myb to E2F4/DP1/p130. The results suggest a model for p53-dependent transcriptional repression by which p53 directly activates p21(WAF1/CIP1). The inhibitor then prevents further phosphorylation of p130 by cyclin-dependent kinases. The presence of hypophosphorylated pocket proteins shifts the equilibrium for complex formation from MMB to DREAM. In the case of promoters that do not hold CDE or E2F elements, binding of DREAM and MMB solely relies on a CHR site. Thus, p53 can repress target genes indirectly through CHR elements.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
p53
B-Myb
Repressor
Biology
Protein complex binding
Mice
Cell Cycle News & Views
Animals
Humans
DREAM complex
Cyclin B2
E2F
Molecular Biology
E2F4
p130
G2 arrest
p21
Cell Cycle
Kv Channel-Interacting Proteins
Promoter
Cell Biology
MuvB
Cell cycle
HCT116 Cells
Molecular biology
Cell Cycle Gene
Repressor Proteins
pRb
Doxorubicin
NIH 3T3 Cells
DNA damage
Tumor Suppressor Protein p53
MMB/DREAM
repression
Protein Binding
Developmental Biology
Subjects
Details
- ISSN :
- 15514005 and 15384101
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cell Cycle
- Accession number :
- edsair.doi.dedup.....6b1b2a77c12441d3ea72a22a3db37537