BID regulation by p53 contributes to chemosensitivity
Abstract
The role of the p53 protein (encoded by TP53) in tumour suppression relies partly on the ability of p53 to regulate the transcription of genes that are important in cell-cycle arrest and in apoptosis. But the apoptotic pathway mediated by p53 is not fully understood. Here we show that BID, a member of the pro-apoptotic Bcl-2 family of proteins, is regulated by p53. BID mRNA is increased in a p53-dependent manner in vitro and in vivo, with strong expression in the splenic red pulp and colonic epithelium of gamma-irradiated mice. Both the human and the mouse BID genomic loci contain p53-binding DNA response elements that bind p53 and mediate p53-dependent transactivation of a reporter gene. In addition, BID-null mouse embryonic fibroblasts are more resistant than are wild-type fibroblasts to the DNA damaging agent adriamycin and the nucleotide analogue 5-fluorouracil, both of which stabilize endogenous p53. Our results indicate that BID is a p53-responsive 'chemosensitivity gene' that may enhance the cell death response to chemotherapy.
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BCL2 and BID are reported as p53 targets but are not directly regulated by p53 according to meta-analysis data.
“Additional BCL-2 family members reported as p53 targets include BCL2190, 191 and BID192—but these are not directly regulated by p53 according to meta-analysis data18 (Supplementary Table S2).”
From Census and evaluation of p53 target genes (2017) · cites this paper as [192]
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- Authors
- Sax, J. K., Fei, P., Murphy, M. E., Bernhard, E., Korsmeyer, S. J., & El-Deiry, W. S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Fox Chase Cancer Center (US)
- University of Pennsylvania (US)
- Venue
- Nature Cell Biology
- Published
- 2002-10-28
- Volume
- 4
- Issue
- 11
- Pages
- 842-849
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1997054509
- Cited by
- 420
- References
- 50
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 12 · 2020: 14 · 2019: 13 · 2018: 12 · 2017: 15 · 2016: 19 · 2015: 10 · 2014: 21 · 2013: 17 · 2012: 19
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- 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
- Bid, p53, chemosensitivity, apoptosis, Bcl-2 family proteins, transcriptional regulation, doxorubicin resistance, 5-fluorouracil resistance, DNA damage response
- MeSH terms
- Adenoviridae, Animals, Carrier Proteins, Cell Line, Cell Separation, Chromatin, Colon, DNA Damage, Doxorubicin, Coloring Agents, Epithelium, Female, Fibroblasts, Flow Cytometry, Fluorouracil, Gamma Rays, Gene Expression Regulation, Humans, Luciferases, Models, Genetic, Plasmids, Precipitin Tests, Protein Conformation, RNA, Messenger, Spleen, Temperature, Transcription, Genetic, Blotting, Northern, Blotting, Western, Tumor Suppressor Protein p53, Cell Death, Apoptosis, Annexin A5, In Situ Hybridization, DNA, Complementary, Oligonucleotide Array Sequence Analysis, BH3 Interacting Domain Death Agonist Protein, Mice
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