The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53
Open accessAbstract
The RING finger proteins HdmX and Hdm2 share significant structural and functional similarity. Hdm2 is a member of the RING finger family of ubiquitin-protein ligases E3 and targets the tumor suppressor protein p53 for degradation. Although HdmX also binds to p53, HdmX does not induce p53 degradation. Moreover, HdmX has been reported to interfere with p53 degradation in overexpression experiments. To obtain insight into the mechanism by which HdmX interferes with p53 degradation, we studied the effect of HdmX on the E3 activity of Hdm2 in vitro. Surprisingly, this revealed that HdmX stimulates Hdm2-mediated ubiquitination of p53 and that HdmX facilitates ubiquitination of Hdm2 and vice versa. In addition, down-regulation of HdmX expression within cells results in the accumulation of both p53 and Hdm2. Because HdmX alone does not have appreciable E3 activity, these data indicate that HdmX acts as a stimulator, rather than as an inhibitor, of the E3 activity of Hdm2 and that, at least under certain conditions, HdmX is actively involved in the degradation of both p53 and Hdm2.
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In the citing paper
“Mdm4 further contributes to Mdm2 stability by disrupting self-ubiquitination of the latter (Stad et al., 2001), while also stimulating Mdm2-mediated polyubiquitination of p53 (Linares et al., 2003).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Linares et al., 2003
In the citing paper
“Despite conservation of the C2H2C4 RING domain, Mdmx shows little intrinsic ubiquitin ligase activity towards p53 [10].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [10]
In the citing paper
“Together with the observation that the Mdm2–Mdmx hetero-oligomer is a more effective ligase for p53 in vitro than Mdm2 alone [10], this has led to a model in which the Mdm2–Mdmx ligase complex is more efficient in targeting p53 for ubiquitylation and degradation.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [10]
In the citing paper
“By contrast, MDMX does not homo-oligomerize and has no intrinsic ubiquitin ligase function, although it can increase or decrease MDM2 ubiquitin ligase activity depending on MDMX abundance16.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [16]
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Citations
Cites
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Metadata
- Authors
- Linares, L. K., Hengstermann, A., Ciechanover, A., Müller, S., & Scheffner, M.
- Affiliations
- Center for Biochemistry, Medical Faculty, and Center for Molecular Medicine, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany; and Department of Biochemistry and The Rappaport Family Institute for Research in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel
- Technion – Israel Institute of Technology (IL)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-09-24
- Volume
- 100
- Issue
- 21
- Pages
- 12009-12014
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC218704
- OpenAlex
- W2046135777
- Cited by
- 361
- References
- 38
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 5 · 2023: 11 · 2022: 15 · 2021: 17 · 2020: 17 · 2019: 14 · 2018: 10 · 2017: 16 · 2016: 16 · 2015: 12 · 2014: 30 · 2013: 19 · 2012: 30
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- KOPS (University of Konstanz) (submittedVersion)
- Funders
- German-Israeli Foundation for Scientific Research and Development
- 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 degradation, ubiquitination, E3 ubiquitin ligase, RING finger protein, protein degradation, tumor suppressor, protein-protein interaction, p53 accumulation
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cell Line, Humans, Molecular Sequence Data, Nuclear Proteins, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Transfection, Tumor Suppressor Protein p53, Ubiquitin, RNA, Small Interfering, Ubiquitin-Protein Ligases, Proto-Oncogene Proteins c-mdm2, In Vitro Techniques
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