The DOI matches its Crossref record; 253 of the 255 references it cites were found in a registry or an index.
Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3
Open accessAbstract
The MDM2 homolog MDMX is an important regulator of p53 during mouse embryonic development. DNA damage promotes MDMX phosphorylation, nuclear translocation, and degradation by MDM2. Here we show that MDMX copurifies with 14-3-3, and DNA damage stimulates MDMX binding to 14-3-3. Chk2-mediated phosphorylation of MDMX on S367 is important for stimulating 14-3-3 binding, MDMX nuclear import by a cryptic nuclear import signal, and degradation by MDM2. Mutation of MDMX S367 inhibits ubiquitination and degradation by MDM2, and prevents MDMX nuclear import. Expression of 14-3-3 stimulates the degradation of phosphorylated MDMX. Chk2 and 14-3-3 cooperatively stimulate MDMX ubiquitination and overcome the inhibition of p53 by MDMX. These results suggest that MDMX-14-3-3 interaction plays a role in p53 response to DNA damage by regulating MDMX localization and stability.
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“Additionally, phosphorylation of Mdm2 and Mdmx at serine residues close to the RING domain by ATM or ATM-dependent kinases leads to accelerated auto-degradation of both Mdm2 [54] and Mdmx [41,55–58], with consequent p53 accumulation and activation.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [56]
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The p53 orchestra: Mdm2 and Mdmx set the tone
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Metadata
- Authors
- LeBron, C., Chen, L., Gilkes, D. M., & Chen, J.
- Affiliations
- Moffitt Cancer Center (US)
- Corresponding author
- Chen, Jiandong
- Venue
- The EMBO Journal
- Published
- 2006-03-02
- Volume
- 25
- Issue
- 6
- Pages
- 1196-1206
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1422166
- OpenAlex
- W2068624303
- Cited by
- 122
- References
- 255
- Citations by year
- 2025: 2 · 2024: 3 · 2022: 1 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 8 · 2015: 2 · 2014: 7 · 2013: 11 · 2012: 9
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - University of South Florida (University of South Florida) (submittedVersion)
- Funders
- American Cancer Society
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- MDMX, Chk2, MDM2, p53, DNA damage response, nuclear import, protein degradation, ubiquitination, phosphorylation, nuclear import signal, protein stability, mouse embryo development
- MeSH terms
- Animals, Breast Neoplasms, DNA Damage, Gene Expression Regulation, HeLa Cells, Humans, Nuclear Proteins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins, Osteosarcoma, Tumor Suppressor Protein p53, Mice, Knockout, Cell Cycle Proteins, Active Transport, Cell Nucleus, Ubiquitin, Immunoprecipitation, 14-3-3 Proteins, Cyclin-Dependent Kinase 2, Mice
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