Transcriptional modulation induced by ionizing radiation: p53 remains a central player
Open accessAbstract
The cellular response to DNA damage is vital for maintaining genomic stability and preventing undue cell death or cancer formation. The DNA damage response (DDR), most robustly mobilized by double‐strand breaks (DSBs), rapidly activates an extensive signaling network that affects numerous cellular systems, leading to cell survival or programmed cell death. A major component of the DDR is the widespread modulation of gene expression. We analyzed together six datasets that probed transcriptional responses to ionizing radiation (IR) – our novel experimental data and 5 published datasets – to elucidate the scope of this response and identify its gene targets. According to the mRNA expression profiles we recorded from 5 cancerous and non‐cancerous human cell lines after exposure to 5 Gy of IR, most of the responses were cell line‐specific. Computational analysis identified significant enrichment for p53 target genes and cell cycle‐related pathways among groups of up‐regulated and down‐regulated genes, respectively. Computational promoter analysis of the six datasets disclosed that a statistically significant number of the induced genes contained p53 binding site signatures. p53‐mediated regulation had previously been documented for subsets of these gene groups, making our lists a source of novel potential p53 targets. Real‐time qPCR and chromatin immunoprecipitation (ChIP) assays validated the IR‐induced p53‐dependent induction and p53 binding to the respective promoters of 11 selected genes. Our results demonstrate the power of a combined computational and experimental approach to identify new transcriptional targets in the DNA damage response network.
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p53 activates PGF, TGFA and KITLG that encode growth factors that can stimulate cell proliferation.
“Notably, p53 also activates PGF,160 TGFA161 and KITLG50 that encode for growth factors that can stimulate cell proliferation.”
From Census and evaluation of p53 target genes (2017) · cites this paper as [160]
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- Authors
- Rashi‐Elkeles, S., Elkon, R., Shavit, S., Lerenthal, Y., Linhart, C., Kupershtein, A., Amariglio, N., Rechavi, G., Shamir, R., & Shiloh, Y.
- Affiliations
- Tel Aviv University (IL)
- Sheba Medical Center (IL)
- Corresponding author
- Rashi‐Elkeles, Sharon
- Venue
- Molecular Oncology
- Publisher
- Wiley
- Published
- 2011-07-07
- Volume
- 5
- Issue
- 4
- Pages
- 336-348
- ISSN
- 1574-7891 (ISSN-L)
- 1878-0261
- PMC
- PMC5528315
- OpenAlex
- W1969093811
- Cited by
- 95
- References
- 95
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 3 · 2022: 1 · 2021: 7 · 2020: 10 · 2019: 5 · 2018: 4 · 2017: 9 · 2016: 5 · 2015: 8 · 2014: 14 · 2013: 17 · 2012: 7
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- European Community’s Seventh Framework Program (HEALTH-F4-2009-223575)
- Israel Science Foundation
- The European Community’s Seventh Framework Program (HEALTH-F4-2007-200767)
- The Israel Cancer Research Fund
- A-T Medical Research Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- ionizing radiation, DNA damage response, p53, transcriptional regulation, p53 target genes, DNA double-strand breaks, cell cycle pathway, promoter analysis, p53 binding sites, mRNA expression profiles, human cell lines, genome stability
- MeSH terms
- DNA Damage, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Radiation, Ionizing, Transcription, Genetic, Meta-Analysis as Topic, Signal Transduction, Tumor Suppressor Protein p53, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Databases, Genetic, Cell Line, Tumor, Gene Regulatory Networks
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