The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding site
Abstract
KILLER/DR5, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor gene, has been shown to be induced by DNA damaging agents and radiation in a p53-dependent manner. Although TRAIL is a potential therapeutic agent for cancer, the induction mechanism of its receptors is poorly understood. Here we show the identification of three p53 DNA-binding sites in the KILLER/DR5 genomic locus located upstream (BS1; -0.82 Kb) of the ATG site, within Intron 1 (BS2; +0.25 Kb downstream of the ATG) and within Intron 2 (BS3; +1.25 Kb downstream of the ATG). A modified p53-binding and immunoselection protocol using a wild-type p53-expressing adenovirus vector (Ad-p53) was used to identify the binding sites and to show that each binding site can bind specifically to wild-type p53 protein (wt-p53). A reporter assay revealed that only BS2 could enhance luciferase expression driven by a basal promoter. We constructed a reporter plasmid carrying the genomic regulatory region of KILLER/DR5 including the three p53 DNA-binding sites but no additional basal promoter. The genomic fragment showed basal transcriptional activity which was induced by wt-p53 but not by mutant p53, and human papilloma virus E6 inhibited the p53-dependent activation. Mutation of BS2 abrogated not only the binding activity of wt-p53 but also the induction of the KILLER/DR5 genomic promoter-reporter gene, indicating that BS2 is responsible for the p53-dependent transactivation of KILLER/ DR5. In p53-wild-type but not -mutant or -null cell lines, doxorubicin treatment stabilized p53 protein, and increased specific binding to BS2 as revealed by EMSA, and upregulated the KILLER/DR5 promoter-luciferase reporter gene. These results suggest that the transactivation of KILLER/DR5 is directly regulated by exogenous or endogenous wt-p53 and establishes KILLER/DR5 as a p53 target gene that can signal apoptotic death.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“TNF receptors include the p53-induced targets FAS47, 48, 49 and TNFRSF10A–D;38, 39 these can be activated by external stimuli such as binding with FASL or TNF-α, thereby leading to caspase-dependent apoptosis.178”
From Census and evaluation of p53 target genes (2017) · cites this paper as [38]
Citations
Cites
Green, D. R., & Reed, J. C. (1998) · Science · doi:10.1126/science.281.5381.1309 · Cited by 9,051
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321
Self-citationDeath Receptors: Signaling and Modulation
Ashkenazi, A., & Dixit, V. M. (1998) · Science · doi:10.1126/science.281.5381.1305 · Cited by 5,866
Nagata, S. (1997) · Cell · doi:10.1016/s0092-8674(00)81874-7 · Cited by 4,934
Tumor suppressor p53 is a direct transcriptional activator of the human bax gene
Toshiyuki, M., & Reed, J. C. (1995) · Cell · doi:10.1016/0092-8674(95)90412-3 · Cited by 4,063
Kastan, M. B., Zhan, Q., El-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., Plunkett, B. S., Vogelstein, B., & Fornace, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90593-2 · Cited by 3,047
Self-citationp53-dependent apoptosis modulates the cytotoxicity of anticancer agents
Lowe, S. W., Ruley, H. E., Jacks, T., & Housman, D. E. (1993) · Cell · doi:10.1016/0092-8674(93)90719-7 · Cited by 2,911
Identification and characterization of a new member of the TNF family that induces apoptosis
Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C.-P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., Rauch, C., Smith, C. A., et al. (1995) · Immunity · doi:10.1016/1074-7613(95)90057-8 · Cited by 2,900
A model for p53-induced apoptosis
Polyak, K., Xia, Y., Zweier, J. L., Kinzler, K. W., & Vogelstein, B. (1997) · Nature · doi:10.1038/38525 · Cited by 2,500
Definition of a consensus binding site for p53
El-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., & Vogelstein, B. (1992) · Nature Genetics · doi:10.1038/ng0492-45 · Cited by 1,985
Self-citation
Cited by
Sorted by citations
Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy
Fulda, S., & Debatin, K.-M. (2006) · Oncogene · doi:10.1038/sj.onc.1209608 · Cited by 2,312
Transcriptional control of human p53-regulated genes
Riley, T., Sontag, E., Chen, P., & Levine, A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2395 · Cited by 1,921
Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971
Yamaguchi, H., & Wang, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406933200 · Cited by 825
From bench to clinic with apoptosis-based therapeutic agents
Nicholson, D. W. (2000) · Nature · doi:10.1038/35037747 · Cited by 685
Metadata
- Authors
- Takimoto, R., & El-Deiry, W. S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Oncogene
- Published
- 2000-03-30
- Volume
- 19
- Issue
- 14
- Pages
- 1735-1743
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2053301688
- Cited by
- 360
- References
- 39
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 12 · 2022: 5 · 2021: 6 · 2020: 11 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 8 · 2015: 10 · 2014: 12 · 2013: 8 · 2012: 18
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Japan Health Sciences Foundation
- National Cancer Institute (P01CA075138, P01 CA75138-01)
- 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 › Genomics and Chromatin Dynamics
- Keywords
- p53, DR5, TRAIL, p53 target genes, intronic enhancer, transcriptional activation, doxorubicin, p53 stabilization, apoptosis, E6 oncoprotein
- MeSH terms
- Binding Sites, DNA, DNA Damage, Doxorubicin, Humans, Introns, Oncogene Proteins, Viral, Promoter Regions, Genetic, Tumor Cells, Cultured, Transcriptional Activation, Gene Expression, Tumor Suppressor Protein p53, Mutagenesis, Apoptosis, Genes, Reporter, Receptors, Tumor Necrosis Factor, Receptors, TNF-Related Apoptosis-Inducing Ligand
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
