Hdmx Stabilizes Mdm2 and p53
Open accessAbstract
The Mdm2 protein is a key regulator of p53 activity and stability. Upon binding, Mdm2 inhibits the transcription regulatory activity of p53 and promotes its rapid degradation. In this study we investigated the effect of the human Mdm2 homologue Hdmx on p53 stability. We found that Hdmx does not target p53 for degradation, although, like Mdm2, it inhibits p53-mediated transcription activation. On the contrary, Hdmx was found to counteract the degradation of p53 by Mdm2, and to stabilize both p53 and Mdm2. The RING finger of Hdmx was found to be necessary and sufficient for this stabilization, and it probably involves hetero-oligomerization with the RING finger of Mdm2, which may lead to inhibition of Mdm2's ubiquitin ligase activity. However, Hdmx does not relieve the inhibition by Mdm2 of transcription activation by p53, probably due to the formation of a trimeric complex consisting of Hdmx, Mdm2, and p53. We propose a model in which Hdmx secures a pool of largely inactive p53, which, upon the induction of stress, can be quickly activated.
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Mdmx does not target p53 for degradation but instead stabilizes p53 and Mdm2.
“However, Mdmx does not target p53 for degradation but even prevents Mdm2-mediated degradation of p53 and also stabilizes Mdm2 (Sharp et al., 1999;Jackson and Berberich, 2000;Stad et al., 2000).”
From Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms (2001) · cites this paper as Stad et al., 2000
Mdmx and Mdm2 interact via their RING finger domains.
“Mdmx and Mdm2 interact via their RING finger domains (Sharp et al., 1999;Stad et al., 2000)”
From Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms (2001) · cites this paper as Stad et al., 2000
The RING finger of Mdmx is needed for stabilization of p53.
“Since the RING finger of Mdmx is needed for stabilization of p53”
From Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms (2001) · cites this paper as Stad et al., 2000
p53, Mdm2 and Mdmx can form a trimeric complex.
“p53, Mdm2 and Mdmx can form a trimeric complex (Stad et al., 2000).”
From Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms (2001) · cites this paper as Stad et al., 2000
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Self-citation
- Authors
- Stad, R., Ramos, Y. F. M., Little, N., Grivell, S., Attema, J., van der Eb, A. J., & Jochemsen, A. G.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Jochemsen, Aart G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 275
- Issue
- 36
- Pages
- 28039-28044
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2043182996
- Cited by
- 145
- References
- 31
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 9 · 2013: 1 · 2012: 8
- FWCI
- 4.70
- 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 stabilization, ring finger, ubiquitin ligase activity, protein degradation, transcriptional activation, hetero-oligomerization, trimeric complex
- MeSH terms
- Humans, Nuclear Proteins, Proto-Oncogene Proteins, Recombinant Proteins, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Zinc Fingers, Proto-Oncogene Proteins c-mdm2
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