Mdm2 is critically and continuously required to suppress lethal p53 activity in vivo
Open accessAbstract
There is currently much interest in the idea of restoring p53 activity in tumor cells by inhibiting Hdm2/Mdm2. However, it has remained unclear whether this would also activate p53 in normal cells. Using a switchable endogenous p53 mouse model, which allows rapid and reversible toggling of p53 status between wild-type and null states, we show that p53 is spontaneously active in all tested tissues of mdm2-deficient mice, triggering fatal pathologies that include ablation of classically radiosensitive tissues. In apoptosis-resistant tissues, spontaneous unbuffered p53 activity triggers profound inhibition of cell proliferation. Such acute spontaneous p53 activity occurs in the absence of any detectable p53 posttranslational modification, DNA damage, or p19ARF signaling and triggers rapid p53 degradation.
Integrity signals
Registry
Cites
Statistics
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?
Mdm2 and Mdmx contribute to p53 regulation to different extents in different tissues in vivo.
“Mdm2 and Mdmx seem to contribute to p53 regulation to different extents in different tissues in vivo (Table 1; [32–40]).”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [36]
In some tissues and cell types, such as the central nervous system and proliferative intestinal cells, there is a requirement for both Mdm2 and Mdmx.
“Clearly in some tissues and cell types [such as the central nervous system (CNS) and proliferative intestinal cells], there is a requirement for both Mdm2 and Mdmx.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [36]
In smooth muscle cells, loss of Mdmx has no phenotype.
“However, in other cases, such as smooth muscle cells, loss of Mdmx has no phenotype.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [36]
Deletion of Mdm2 can cause p53 activation in both tumour tissue and normal tissue.
“Although deletion of Mdm2 can cause p53 activation in both tumour tissue and normal tissue81”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [81]
The citation lists haven’t been fetched yet
References 61 · Cited by 256
- Authors
- Ringshausen, I., O'Shea, C. C., Finch, A. J., Swigart, L. B., & Evan, G. I.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 10
- Issue
- 6
- Pages
- 501-514
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2119312052
- Cited by
- 256
- References
- 61
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 8 · 2023: 13 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 6 · 2018: 6 · 2017: 12 · 2016: 12 · 2015: 8 · 2014: 20 · 2013: 15 · 2012: 23
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- Deutsche Krebshilfe
- National Institutes of Health (1r21ag025413-01)
- University of California, San Francisco
- National Institute on Aging (AG025413)
- National Cancer Institute (CA10013)
- 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
- MDM2, p53, p53 degradation, radiosensitivity, apoptosis resistance, cell proliferation inhibition, p19ARF, tumor suppression
- MeSH terms
- Animals, DNA Damage, Imidazoles, Phosphorylation, Piperazines, Tamoxifen, Transcription, Genetic, Tumor Suppressor Protein p53, ADP-Ribosylation Factor 1, Mice, 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
