The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
MDMX regulation of p53 response to ribosomal stress
Open accessAbstract
Ribosomal stress such as disruption of rRNA biogenesis activates p53 by release of ribosomal proteins from the nucleoli, which bind to MDM2 and inhibit p53 degradation. We found that p53 activation by ribosomal stress requires degradation of MDMX in an MDM2-dependent fashion. Tumor cells overexpressing MDMX are less sensitive to actinomycin D-induced growth arrest due to formation of inactive p53-MDMX complexes. Knockdown of MDMX increases sensitivity to actinomycin D, whereas MDMX overexpression abrogates p53 activation and prevents growth arrest. Furthermore, MDMX expression promotes resistance to the chemotherapeutic agent 5-fluorouracil (5-FU), which at low concentrations activates p53 by inducing ribosomal stress without significant DNA damage signaling. Knockdown of MDMX abrogates HCT116 tumor xenograft formation in nude mice. MDMX overexpression does not accelerate tumor growth but increases resistance to 5-FU treatment in vivo. Therefore, MDMX is an important regulator of p53 response to ribosomal stress and RNA-targeting chemotherapy agents.
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“However, both Mdm2 and Mdmx interact with many other proteins, including those involved in development, morphogenesis and tumorigenesis (Table 2; [81–92]).”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [88]
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Metadata
- Authors
- Gilkes, D. M., Chen, L., & Chen, J.
- Affiliations
- Moffitt Cancer Center (US)
- Corresponding author
- Chen, Jiandong
- Venue
- The EMBO Journal
- Published
- 2006-11-16
- Volume
- 25
- Issue
- 23
- Pages
- 5614-5625
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1679771
- OpenAlex
- W2119121049
- Cited by
- 142
- References
- 57
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 9 · 2015: 4 · 2014: 9 · 2013: 12 · 2012: 14
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- University of South Florida
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- MDMX, p53, ribosomal stress, rRNA biogenesis, MDM2, p53 degradation, ribosomal proteins, nucleolus, actinomycin D, 5-fluorouracil, chemoresistance, tumor xenografts, growth arrest
- MeSH terms
- Animals, Antineoplastic Agents, Dactinomycin, DNA Damage, Female, Fluorouracil, Humans, Mice, Nude, Neoplasms, Nuclear Proteins, Proto-Oncogene Proteins, Ribosomal Proteins, Ribosomes, RNA, Ribosomal, Tumor Suppressor Protein p53, Cell Cycle Proteins, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, Cell Line, Tumor, Cell Proliferation, Mice, Proto-Oncogene Proteins c-mdm2
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