Cited by 110Cancer-related Molecular PathwaysGenomics and Chromatin DynamicsSignaling Pathways in Disease

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p130/E2F4 Binds to and Represses the cdc2 Promoter in Response to p53

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Taylor, William R., Schönthal, Axel H., Galante, Jeanna, Stark, George R.·2001·Journal of Biological Chemistry

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Abstract

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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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.
ORCID: Taylor, William R.
Schönthal, Axel H.
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)
DOI: 10.1074/jbc.m005101200
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7226 d)
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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p130/E2F4 Binds to and Represses the cdc2 Promoter in Response to p53

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