The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Hdmx Protein Stability Is Regulated by the Ubiquitin Ligase Activity of Mdm2
Open accessAbstract
The stability of the p53 tumor suppressor protein is critically regulated by the Hdm2 and Hdmx proteins. Hdm2 protein levels are auto-regulated by the self-ubiquitination activity of Hdm2 and on the transcriptional level by p53-activated transcription of the hdm2 gene. Little is known about the regulation of Hdmx expression levels, apart from the observation that the Mdmx protein can be cleaved by caspase-3 in a p53-inducible manner. In the functional analysis of two mutant Hdmx proteins, products of two alternatively spliced mRNAs, it was found that Hdmx proteins are targets for ubiquitination by Mdm2. The stability of the Hdmx protein is partly dependent on the presence of its internal acidic domain. Mdm2 appears only to require an intact RING domain to be able to ubiquitinate Hdmx and target it for proteasomal degradation. These findings highlight the intricate functional relationships between p53, Mdm2, and Hdmx.
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“However, in addition to degrading p53, Mdm2 also undergoes auto-degradation [12,13] and targets Mdmx for degradation [14–16], which is critical for optimal p53 activation after stress.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [14]
In the citing paper
“Several reports showed that MDMX can be ubiquitinated and degraded by MDM2 (De Graaf et al, 2003;Kawai et al, 2003;Pan and Chen, 2003).”
From ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage (2005) · cites this paper as De Graaf et al, 2003
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Research works printed but not linked: 3
- Riemenschneider, 1999, Cancer Res., 59, 6091
- Ramos, 2001, Cancer Res., 61, 1839
- Chen, 1993, Mol. Cell. Biol., 13, 4107
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Colacurcio, D. J., Yeager, A. M., Kolson, D. L., Jordan‐Sciutto, K. L., & Akay, C. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2013.10.003 · Cited by 11
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Wohlberedt, K. (2024) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-10645
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Malhab, L. J. B., Schmidt, S., Fagotto‐Kaufmann, C., Pion, E., Gadéa, G., Roux, P., Fagotto, F., Debant, A., & Xirodimas, D. P. (2024) · Cells · doi:10.3390/cells13191625
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Background
Metadata
- Authors
- de Graaf, P., Little, N. A., Ramos, Y. F. M., Meulmeester, E., Letteboer, S. J. F., & Jochemsen, A. G.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Jochemsen, Aart G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 278
- Issue
- 40
- Pages
- 38315-38324
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2163552821
- Cited by
- 143
- References
- 52
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 3 · 2012: 8
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- HDMX, MDM2, p53, protein stability, ubiquitination, ubiquitin ligase activity, RING domain, proteasomal degradation, alternative splicing, caspase-3 cleavage, acidic domain, tumor suppressor regulation
- MeSH terms
- Cycloheximide, Exons, Genetic Vectors, Humans, Lac Operon, Ligases, Luciferases, Microscopy, Fluorescence, Models, Genetic, Nuclear Proteins, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Protein Synthesis Inhibitors, Proto-Oncogene Proteins, RNA, RNA, Messenger, Time Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Blotting, Western, Tumor Suppressor Protein p53, Alternative Splicing, Protein Structure, Tertiary, Reverse Transcriptase Polymerase Chain Reaction, Caspases, Ubiquitin, Proto-Oncogene Proteins c-mdm2, Caspase 3
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