Mdm2 affects genome stability independent of p53
Abstract
Mdm2 is a critical negative regulator of the p53 tumor suppressor and is frequently overexpressed in human cancers. However, reports, including our own studies, suggest that Mdm2 has both p53-dependent and p53-independent functions that contribute to genomic instability and transformation when deregulated. We recently elucidated a p53-independent role for Mdm2 in the regulation of the DNA double-strand break repair response, genomic stability, and transformation through interaction with Nbs1, a member of the Mre11/Rad50/Nbs1 DNA double-strand break repair complex. In light of these findings, targeting Mdm2 in human malignancies may have effects other than activating p53. [Cancer Res 2009;69(5):1697–701]
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The Mdm2-Nbs1 interaction coupled with increased chromatid breaks due to increased Mdm2 levels can be a causative mechanism for p53-independent genomic instability and cellular transformation.
“The authors point out that this unique interaction coupled with increased chromatid breaks due to increased Mdm2 protein levels can be one causative mechanism for p53-independent genomic instability and cellular transformation [33].”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [33]
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- Authors
- Bouska, A., & Eischen, C. M.
- Affiliations
- University of Nebraska Medical Center (US)
- Vanderbilt University (US)
- Venue
- Cancer Research
- Published
- 2009-03-01
- Volume
- 69
- Issue
- 5
- Pages
- 1697-1701
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2056163313
- Semantic Scholar
- 4a01dd868d3a869e6fdf674863e44306c6cec7cd
- Cited by
- 71
- References
- 27
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 2 · 2015: 3 · 2014: 7 · 2013: 3 · 2012: 8
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA117935, CA098139, CA117935, R01CA098139)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- MDM2, p53-independent function, genomic instability, DNA double-strand break repair, NBS1, Mre11-Rad50-Nbs1 complex, tumor suppressor regulation, cancer transformation
- MeSH terms
- Animals, Cell Transformation, Neoplastic, DNA Repair, Humans, Neoplasms, Nuclear Proteins, Tumor Suppressor Protein p53, Cell Cycle Proteins, Genomic Instability, Proto-Oncogene Proteins c-mdm2, DNA Breaks, Double-Stranded
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