Cited by 1,801Cancer-related Molecular PathwaysHeat shock proteins researchCell death mechanisms and regulation

The p53-mdm-2 autoregulatory feedback loop.

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Wu, X, Bayle, J H, Olson, D, Levine, A J·1993·Genes & Development

Abstract

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.

    “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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Authors
Wu, X., Bayle, J. H., Olson, D., & Levine, A. J.
Affiliations
Princeton University (US)
Venue
Genes & Development
Published
1993-07-01
Volume
7
Issue
7a
Pages
1126-1132
ISSN
0890-9369 (ISSN-L)
OpenAlex
W2170494099
Cited by
1,801
References
41
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
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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