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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In the citing paper
“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
Citations
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Mdm2 promotes the rapid degradation of p53
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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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Sorted by citations
Awakening guardian angels: drugging the p53 pathway
Brown, C. J., Lain, S., Verma, C. S., Fersht, A. R., & Lane, D. P. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2763 · Cited by 881
“Another consequence of MDM2–MDM4 heterodimerization is that MDM4 can be ubiquitylated by MDM2and is consequently degrade”
BackgroundMoll, U. M., & Petrenko, O. (2003) · PubMed · Cited by 778
IAPs, RINGs and ubiquitylation
Vaux, D. L., & Silke, J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1621 · Cited by 626
Coping with stress: multiple ways to activate p53
Horn, H. F., & Vousden, K. H. (2007) · Oncogene · doi:10.1038/sj.onc.1210263 · Cited by 522
“…(Sharp et al., 1999; Tanimura et al., 1999), which results in the stabilization of Mdm2 (Stad et al., 2001; Gu et al., 2002) or the Mdm2-mediated degradation of MdmX (de Graaf et al., 2003; Kawai et al., 2003; Pan and Chen, 2003), depending on the relative expression levels of the two proteins.”
BackgroundThe p53 orchestra: Mdm2 and Mdmx set the tone
Wade, M., Wang, Y. V., & Wahl, G. M. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.01.009 · Cited by 450
“However, in addition to degrading p53, Mdm2 also undergoes autodegradation [12,13] and targets Mdmx for degradation [14–16], which is critical for optimal Wade et al.”
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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