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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.
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“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]
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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
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