The DOI matches its Crossref record; 52 of the 54 references it cites were found in a registry or an index.
The RING Domain of Mdm2 Mediates Histone Ubiquitylation and Transcriptional Repression
Open accessAbstract
Histone modifications play a pivotal role in regulating transcription and other chromatin-associated processes. In yeast, histone H2B monoubiquitylation affects gene silencing. However, mammalian histone ubiquitylation remains poorly understood. We report that the Mdm2 oncoprotein, a RING domain E3 ubiquitin ligase known to ubiquitylate the p53 tumor suppressor protein, can interact directly with histones and promote in vitro monoubiquitylation of histones H2A and H2B. Moreover, Mdm2 induces H2B monoubiquitylation in vivo. Endogenous Mdm2 is tethered in vivo, presumably via p53, to chromatin comprising the p53-responsive p21(waf1) promoter, and Mdm2 overexpression enhances protein ubiquitylation in the vicinity of a p53 binding site within that promoter. Moreover, when recruited to a promoter in the absence of p53, Mdm2 can repress transcription dependently on its RING domain, suggesting that its E3 activity contributes to repression. Histone ubiquitylation may thus constitute a novel mechanism of transcriptional repression by Mdm2, possibly underlying some of its oncogenic activities.
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“For example, Mdm2 can transcriptionally inactivate some p53 target genes by direct ubiquitylation of histones [109].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [109]
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E3 Ubiquitin ligases molecular strategies against proteostasis defects of imperfect ageing
Upadhyay, A., Joshi, V., Amanullah, A., Mishra, R., Verma, R. K., Adlakha, Y. K., Suresh, A. K., Dhiman, R., Bhattacharyya, S., & Mishra, A. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103319
REGULATION OF MDM2 MEDIATED NFκB2 PATHWAY IN HUMAN LUNG CANCER
Mohanraj, L. (2008) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/3pem-5151
Metadata
- Authors
- Minsky, N., & Oren, M.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Oren, Moshe
- ORCID
- Oren, Moshe
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 16
- Issue
- 4
- Pages
- 631-639
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1999310200
- Cited by
- 204
- References
- 54
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 8 · 2019: 13 · 2018: 6 · 2017: 1 · 2016: 7 · 2015: 13 · 2014: 10 · 2013: 5 · 2012: 12
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R37 CA40099, R37CA040099)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- MDM2, RING domain, E3 ubiquitin ligase, histone ubiquitination, histone H2A, transcriptional repression, p53, chromatin, gene silencing, oncogenic activity
- MeSH terms
- Cell Line, Chromatin, Glutathione Transferase, Histones, Humans, Luciferases, Nuclear Proteins, Precipitin Tests, Promoter Regions, Genetic, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Transcription, Genetic, Ubiquitins, Gene Expression Regulation, Neoplastic, Genes, Reporter, Cell Line, Tumor, Chromatin Immunoprecipitation, Proto-Oncogene Proteins c-mdm2
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