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p130/E2F4 Binds to and Represses the cdc2 Promoter in Response to p53
Open accessAbstract
p53 represses the transcription of cdc2 and cyclin B1, causing loss of Cdc2 activity and G(2) arrest. Here we show that the region -22 to -2 of the cdc2 promoter called the R box is required for repression by p53 but not for basal promoter activity. The R box confers p53-dependent repression on heterologous promoters and binds to p130/E2F4 in response to overexpression of p53. R box-dependent repression requires p21/waf1, and overexpression of p21/waf1 also represses the cdc2 promoter. These observations suggest that p53 represses the cdc2 promoter by inducing p21/waf1, which inhibits cyclin-dependent kinase activity, enhancing the binding of p130 and E2F4, which together bind to and repress the cdc2 promoter.
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“Consistent with this notion, p130 and E2F4 are recruited to cell cycle gene promoters when p21 is activated by p53.98, 99”
From Census and evaluation of p53 target genes (2017) · cites this paper as [98]
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Metadata
- Authors
- Taylor, W. R., Schönthal, A. H., Galante, J., & Stark, G. R.
- Affiliations
- Cleveland Clinic (US)
- University of Southern California (US)
- Corresponding author
- Stark, George R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 276
- Issue
- 3
- Pages
- 1998-2006
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2086565810
- Cited by
- 110
- References
- 89
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM49345, R01GM049345)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- p53, transcriptional repression, p21, cyclin-dependent kinases, G2 cell cycle arrest, E2F4, cyclin B1
- MeSH terms
- Base Sequence, Cell Line, DNA, DNA-Binding Proteins, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding, Repressor Proteins, Transcription Factors, Transcription, Genetic, Tumor Suppressor Protein p53, Protein Serine-Threonine Kinases, Cyclin-Dependent Kinases, CDC2-CDC28 Kinases, E2F4 Transcription Factor, Cyclin-Dependent Kinase 2
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