Cited by 114Cancer-related Molecular PathwaysCell death mechanisms and regulationHeat shock proteins research

Identification of Cell Cycle Regulatory Genes as Principal Targets of p53-mediated Transcriptional Repression

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Spurgers, Kevin B., Gold, David L., Coombes, Kevin R., Bohnenstiehl, Nicole L., Mullins, Brian, Meyn, Raymond E., Logothetis, Christopher J., McDonnell, Timothy J.·2006·Journal of Biological Chemistry

Abstract

Historically, most studies attribute p53 function to the transactivation of target genes. That p53 can selectively repress genes to affect a cellular response is less widely appreciated. Available evidence suggests that repression is important for p53-induced apoptosis and cell cycle arrest. To better establish the scope of p53-repressed target genes and the cellular processes they may affect, a global expression profiling strategy was used to identify p53-responsive genes following adenoviral p53 gene transfer (Ad-p53) in PC3 prostate cancer cells. A total of 111 genes, 0.77% of the 14,500 genes represented on the Affymetrix U133A microarray, were repressed more than 2-fold (p < or = 0.05). Validation of the array data, using reverse transcription-PCR of 20 randomly selected genes, yielded a confirmation rate of >95.5% for the complete data set. Functional over-representation analysis revealed that cell cycle regulatory genes exhibited a highly significant enrichment (p < or = 5 x 10(-28)) within the transrepressed targets. 41% of the repressed targets are cell cycle regulators. A subset of these genes exhibited repression following DNA damage, preceding cell cycle arrest, in LNCaP cells. The use of a p53 small interfering RNA strategy in LNCaP cells and the use of p53-null cell lines demonstrated that this repression is p53-dependent. These findings identify a set of genes not known previously to be down-regulated by p53 and indicate that p53-induced cell cycle arrest is a function of not only the transactivation of cell cycle inhibitors (e.g. p21) but also the repression of targets that regulate proliferation at several distinct phases of the cell cycle.

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Crossref · 10.1074/jbc.m513901200

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  • Most genes downregulated by p53 are cell cycle genes.

    “Genome-wide analyses show that most genes downregulated by p53 are cell cycle genes115”

    From Census and evaluation of p53 target genes (2017) · cites this paper as [115]

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Authors
Spurgers, K. B., Gold, D. L., Coombes, K. R., Bohnenstiehl, N. L., Mullins, B., Meyn, R. E., Logothetis, C. J., & McDonnell, T. J.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
McDonnell, Timothy J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2006-09
Volume
281
Issue
35
Pages
25134-25142
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1992686564
Cited by
114
References
51
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 4 · 2018: 2 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 5 · 2013: 10 · 2012: 9
FWCI
6.41
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (P50 CA 90270, CA-16672, R01 CA69003-9, R01CA069003, P50CA090270, P30CA016672)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
p53, transcriptional repression, cell cycle regulatory genes, p53 target genes, prostate cancer, PC-3 cells, LNCaP cells, DNA damage response, cell cycle arrest, apoptosis, gene expression profiling, siRNA
MeSH terms
Adenoviridae, Cell Cycle, Gene Expression Regulation, Humans, Nucleic Acid Hybridization, Transcription, Genetic, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Cell Line, Tumor, Cell Proliferation

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