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MdmX Protects p53 from Mdm2-Mediated Degradation
Open accessAbstract
The p53 tumor suppressor protein is stabilized in response to cellular stress, resulting in activation of genes responsible for either cell cycle arrest or apoptosis. The cellular pathway for releasing normal cells from p53-dependent cell cycle arrest involves the Mdm2 protein. Recently, a p53-binding protein with homology to Mdm2 was identified and called MdmX. Like Mdm2, MdmX is able to bind p53 and inhibit p53 transactivation; however, the ability of MdmX to degrade p53 has yet to be examined. We report here that MdmX is capable of associating with p53 yet is unable to facilitate nuclear export or induce p53 degradation. In addition, expression of MdmX can reverse Mdm2-targeted degradation of p53 while maintaining suppression of p53 transactivation. Using a series of MdmX deletions, we have determined that there are two distinct domains of the MdmX protein that can stabilize p53 in the presence of Mdm2. One domain requires MdmX interaction with p53 and results in the retention of both proteins within the nucleus and repression of p53 transactivation. The second domain involves the MdmX ring finger and results in stabilization of p53 and an increase in p53 transactivation. The potential basis for stabilization and increased p53 transactivation by the MdmX ring finger domain is discussed. Based on these observations, we propose that the MdmX protein may function to maintain a nuclear pool of p53 protein in undamaged cells.
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“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 Jackson and Berberich, 2000
In the citing paper
“Since Mdmx is unable to shuttle from the nucleus to the cytoplasm (Jackson and Berberich, 2000)”
From Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms (2001) · cites this paper as Jackson and Berberich, 2000
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Self-citation
Flagged first, then by citations
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Cited by
Sorted by citations
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Metadata
- Authors
- Jackson, M. W., & Berberich, S. J.
- Affiliations
- Wright State University (US)
- ORCID
- Jackson, Mark W.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-02-01
- Volume
- 20
- Issue
- 3
- Pages
- 1001-1007
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC85217
- OpenAlex
- W2125124408
- Cited by
- 211
- References
- 35
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 4 · 2014: 11 · 2013: 5 · 2012: 14
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA-64430, R01CA064430, R29CA064430)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- MDMX, p53, MDM2, p53 degradation, p53 stabilization, p53 transactivation, RING domain, nuclear retention, tumor suppressor proteins, cell cycle arrest, apoptosis
- MeSH terms
- Amino Acid Sequence, Animals, Carcinoma, Non-Small-Cell Lung, Cell Line, Cell Nucleus, HeLa Cells, Humans, Lung Neoplasms, Molecular Sequence Data, Nuclear Proteins, Proto-Oncogene Proteins, Recombinant Proteins, Transfection, Tumor Cells, Cultured, Transcriptional Activation, Genes, p53, Tumor Suppressor Protein p53, Sequence Alignment, 3T3 Cells, Sequence Deletion, Sequence Homology, Amino Acid, Mice, Knockout, Mice, Proto-Oncogene Proteins c-mdm2
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