The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
The p53-mdm-2 autoregulatory feedback loop.
Open accessAbstract
The p53 protein can bind to a set of specific DNA sequences, and this may activate the transcription of genes adjacent to these DNA elements. The mdm-2 gene is shown here to contain a p53 DNA-binding site and a genetically responsive element such that expression of the mdm-2 gene can be regulated by the level of wild-type p53 protein. The mdm-2 protein, in turn, can complex with p53 and decrease its ability to act as a positive transcription factor at the mdm-2 gene-responsive element. In this way, the mdm-2 gene is autoregulated. The p53 protein regulates the mdm-2 gene at the level of transcription, and the mdm-2 protein regulates the p53 protein at the level of its activity. This creates a feedback loop that regulates both the activity of the p53 protein and the expression of the mdm-2 gene.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“The best known feedback loop uses MDM2, a p53 target gene that encodes a ubiquitin ligase, which mediates degradation of p53.14, 15, 217”
From Census and evaluation of p53 target genes (2017) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589
Molecular Cloning. A Laboratory Manual
Wood, E. (1983) · Biochemical Education · doi:10.1016/0307-4412(83)90068-7 · Cited by 29,534
A new technique for the assay of infectivity of human adenovirus 5 DNA
Graham, F. L., & van der Eb, A. J. (1973) · Virology · doi:10.1016/0042-6822(73)90341-3 · Cited by 9,302
p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018
The p53 tumour suppressor gene
Levine, A. J., Momand, J. A., & Finlay, C. A. (1991) · Nature · doi:10.1038/351453a0 · Cited by 3,785
Self-citationMomand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113
Self-citationKastan, 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
Association of Human Papillomavirus Types 16 and 18 E6 Proteins with p53
Werness, B. A., Levine, A. J., & Howley, P. M. (1990) · Science · doi:10.1126/science.2157286 · Cited by 2,562
Self-citationT antigen is bound to a host protein in SY40-transformed cells
Lane, D. P., & Crawford, L. V. (1979) · Nature · doi:10.1038/278261a0 · Cited by 2,456
The p53 proto-oncogene can act as a suppressor of transformation
Finlay, C. A., Hinds, P. W., & Levine, A. J. (1989) · Cell · doi:10.1016/0092-8674(89)90045-7 · Cited by 1,987
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–127 of 127
LaRusch, G. A., Jackson, M. W., Dunbar, J. D., Warren, R. S., Donner, D. B., & Mayo, L. D. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2710 · Cited by 89
A distinct p53 target gene set predicts for response to the selective p53–HDM2 inhibitor NVP-CGM097
Jeay, S., Gaulis, S., Ferretti, S., Bitter, H., Ito, M., Valat, T., Murakami, M., Ruetz, S., Guthy, D. A., Rynn, C., et al. (2015) · eLife · doi:10.7554/elife.06498 · Cited by 85
Targeting Therapies for the p53 Protein in Cancer Treatments
Levine, A. J. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030518-055455 · Cited by 84
Self-citationOverexpression of the MDM2 Oncogene in Leukemia and Lymphoma
Watanabe, T., Ichikawa, A., Saito, H., & Hotta, T. (1996) · Leukemia & Lymphoma · doi:10.3109/10428199609093436 · Cited by 80
Regulation of MDMX Expression by Mitogenic Signaling
Gilkes, D. M., Pan, Y., Coppola, D., Yeatman, T., Reuther, G. W., & Chen, J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01633-07 · Cited by 82
Small molecule modulators of protein-protein interactions: selected case studies
Aeluri, M., Chamakuri, S., Dasari, B., Guduru, S. K. R., Jimmidi, R., Jogula, S., & Arya, P. (2014) · Chemical Reviews · doi:10.1021/cr4004049 · Cited by 79
Wang, H., Yu, D., Agrawal, S., & Zhang, R. (2003) · The Prostate · doi:10.1002/pros.10187 · Cited by 78
Targeting the MDM2-p53 protein–protein interaction for new cancer therapeutics
Wang, S., Zhao, Y., Bernard, D., Aguilar, A., & Kumar, S. (2012) · Topics in Medicinal Chemistry · doi:10.1007/978-3-642-28965-1_2 · Cited by 72
Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway
Bang, S., Kaur, S., & Kurokawa, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010261 · Cited by 69
A role of HAUSP in tumor suppression in a human colon carcinoma xenograft model.
Becker, K., Marchenko, N., Palacios, G., & Moll, U. M. (2008) · Cell Cycle · doi:10.4161/cc.7.9.5756 · Cited by 63
Liao, G., Yang, D., Ma, L., Li, W., Hu, L., Zeng, L., Wu, P., Duan, L., & Liu, Z. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.09.044 · Cited by 63
Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy
Zhang, Z., Ding, Q., Liu, J.-J., Zhang, J., Jiang, N., Chu, X.-J., Bartkovitz, D., Luk, K.-C., Janson, C., Tovar, C., et al. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.05.072 · Cited by 60
Phillips, A., Teunisse, A., Lam, S., Lodder, K., Darley, M., Emaduddin, M., Wolf, A., Richter, J., de Lange, J., Verlaan-de Vries, M., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.129726 · Cited by 55
Hoffman-Luca, C. G., Ziazadeh, D., McEachern, D., Zhao, Y., Sun, W., Debussche, L., & Wang, S. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2506 · Cited by 52
Kocik, J., Machula, M., Wisniewska, A., Surmiak, E., Holak, T. A., & Skalniak, L. (2019) · Cancers · doi:10.3390/cancers11071014 · Cited by 46
Identification of a CK2 phosphorylation site in mdm2.
Götz, C., Kartarius, S., Scholtes, P., Nastainczyk, W., & Montenarh, M. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00882.x · Cited by 39
Rubin de Celis, M. F., Garcia-Martin, R., Syed, I., Lee, J., Aguayo-Mazzucato, C., Bonner-Weir, S., & Kahn, B. B. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2206923119 · Cited by 39
Therapeutic inhibition of the MDM2-p53 interaction prevents recurrence of adenoid cystic carcinomas
Nör, F., Warner, K. A., Zhang, Z., Acasigua, G. A., Pearson, A. T., Kerk, S. A., Helman, J. I., Sant'Ana Filho, M., Wang, S., & Nör, J. E. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1235 · Cited by 37
“This interaction is important to maintain low cellular levels of p53 in physiologic conditions (14, 15).”
BackgroundMdmX regulates transformation and chromosomal stability in p53-deficient cells
Matijasevic, Z., Krzywicka-Racka, A., Sluder, G., & Jones, S. N. (2008) · Cell Cycle · doi:10.4161/cc.7.19.6797 · Cited by 34
Stimulation of human DNA polymerase epsilon by MDM2
Asahara, H. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg342 · Cited by 33
Abnormal MDMX degradation in tumor cells due to ARF deficiency
Li, X., Gilkes, D., Li, B., Cheng, Q., Pernazza, D., Lawrence, H., Lawrence, N., & Chen, J. (2012) · Oncogene · doi:10.1038/onc.2011.534 · Cited by 32
Valentin-Vega, Y. A., Box, N., Terzian, T., & Lozano, G. (2009) · Differentiation · doi:10.1016/j.diff.2009.03.001 · Cited by 28
E3 ubiquitin ligases and human papillomavirus-induced carcinogenesis
Lou, Z., & Wang, S. (2014) · Journal of International Medical Research · doi:10.1177/0300060513506655 · Cited by 22
Deregulation of the p14ARF/Mdm2/p53 pathway and G1/S transition in two glioblastoma sets
Ghimenti, C., Fiano, V., Chiadò-Piat, L., Chiò, A., Cavalla, P., & Schiffer, D. (2003) · Journal of Neuro-Oncology · doi:10.1023/a:1022127302008 · Cited by 21
The phenotype of MDM2 auto-degradation after DNA damage is due to epitope masking by phosphorylation
Cheng, Q., & Chen, J. (2011) · Cell Cycle · doi:10.4161/cc.10.7.15249 · Cited by 21
Acetylation: a new target for protein degradation in cancer
Crawford, C. E. W., & Burslem, G. M. (2025) · Trends in Cancer · doi:10.1016/j.trecan.2025.01.013 · Cited by 20
Gollner, A., Rudolph, D., Weyer-Czernilofsky, U., Baumgartinger, R., Jung, P., Weinstabl, H., Ramharter, J., Grempler, R., Quant, J., Rinnenthal, J., et al. (2024) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-23-0783 · Cited by 18
Metadata
- Authors
- Wu, X., Bayle, J. H., Olson, D., & Levine, A. J.
- Affiliations
- Princeton University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1993-07-01
- Volume
- 7
- Issue
- 7a
- Pages
- 1126-1132
- ISSN
- 0890-9369 (ISSN-L)
- OpenAlex
- W2170494099
- Cited by
- 1,801
- References
- 40
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 37 · 2023: 40 · 2022: 38 · 2021: 38 · 2020: 51 · 2019: 34 · 2018: 42 · 2017: 43 · 2016: 50 · 2015: 44 · 2014: 64 · 2013: 44 · 2012: 62
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P01CA041086, P01CA41086)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53, MDM2, autoregulation, feedback loops, transcriptional regulation, gene expression regulation
- MeSH terms
- Animals, Base Sequence, Binding Sites, Cell Line, Cell Line, Transformed, DNA Mutational Analysis, DNA-Binding Proteins, Feedback, Fibroblasts, Homeostasis, Molecular Sequence Data, Mutation, Neoplasm Proteins, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins, RNA, Messenger, Temperature, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Mice, Rats, Proto-Oncogene Proteins c-mdm2
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
