Cullin 3 mediates SRC-3 ubiquitination and degradation to control the retinoic acid response
Open accessAbstract
SRC-3 is an important coactivator of nuclear receptors including the retinoic acid (RA) receptor α. Most of SRC-3 functions are facilitated by changes in the posttranslational code of the protein that involves mainly phosphorylation and ubiquitination. We recently reported that SRC-3 is degraded by the proteasome in response to RA. Here, by using an RNAi E3-ubiquitin ligase entry screen, we identified CUL-3 and RBX1 as components of the E3 ubiquitin ligase involved in the RA-induced ubiquitination and subsequent degradation of SRC-3. We also show that the RA-induced ubiquitination of SRC-3 depends on its prior phosphorylation at serine 860 that promotes binding of the CUL-3–based E3 ligase in the nucleus. Finally, phosphorylation, ubiquitination, and degradation of SRC-3 cooperate to control the dynamics of transcription. In all, this process participates to the antiproliferative effect of RA.
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Phosphorylation marks SRC-3 for ubiquitination and degradation by the proteasome.
“Then phosphorylation marks SRC-3 for ubiquitination and degradation by the proteasome ( 149 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [149]
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Retinoic acid receptors: From molecular mechanisms to cancer therapy
di Masi, A., Leboffe, L., De Marinis, E., Pagano, F., Cicconi, L., Rochette-Egly, C., Lo-Coco, F., Ascenzi, P., & Nervi, C. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.12.003 · Cited by 403 · see citing works
Self-citationVitamin A and retinoid signaling: genomic and nongenomic effects
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- Authors
- Ferry, C., Gaouar, S., Fischer, B., Boeglin, M., Paul, N., Samarut, E., Piskunov, A., Pankotai-Bodo, G., Brino, L., & Rochette-Egly, C.
- Affiliations
- Department of Functional Genomics and Cancer,
- High Throughput Screening Facility,
- Centre National de la Recherche Scientifique (FR)
- Bioinformatics Platform; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-12-06
- Volume
- 108
- Issue
- 51
- Pages
- 20603-20608
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3251120
- OpenAlex
- W2057566218
- Cited by
- 33
- References
- 3
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 5 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 5 · 2012: 2
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-09-BLAN-0297, ANR-05-BLAN-0390)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- SRC-3, CUL3, RBX1, E3 ubiquitin ligase, ubiquitination, protein degradation, retinoic acid receptor alpha, retinoic acid response, nuclear receptor coactivators, proteasome, transcriptional regulation, antiproliferative activity
- MeSH terms
- Animals, Binding Sites, Cell Differentiation, Cell Nucleus, Chlorocebus aethiops, Chromatin, Humans, Microscopy, Fluorescence, Phosphorylation, Transcription, Genetic, Tretinoin, COS Cells, Ubiquitin, Cullin Proteins, Cell Line, Tumor, Cell Proliferation, Nuclear Receptor Coactivator 3
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