SUG-1 Plays Proteolytic and Non-proteolytic Roles in the Control of Retinoic Acid Target Genes via Its Interaction with SRC-3
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Nuclear retinoic acid receptor alpha (RARalpha) activates gene expression through dynamic interactions with coregulatory protein complexes, the assembly of which is directed by the ligand and the AF-2 domain of RARalpha. Then RARalpha and its coactivator SRC-3 are degraded by the proteasome. Recently it has emerged that the proteasome also plays a key role in RARalpha-mediated transcription. Here we show that SUG-1, one of the six ATPases of the 19 S regulatory complex of the 26 S proteasome, interacts with SRC-3, is recruited at the promoters of retinoic acid (RA) target genes, and thereby participates to their transcription. In addition, SUG-1 also mediates the proteasomal degradation of SRC-3. However, when present in excess amounts, SUG-1 blocks the activation of RARalpha target genes and the degradation of RARalpha that occurs in response to RA, via its ability to interfere with the recruitment of SRC-3 and other coregulators at the AF-2 domain of RARalpha. We propose a model in which the ratio between SUG-1 and SRC-3 is crucial for the control of RARalpha functioning. This study provides new insights into how SUG-1 has a unique role in linking the transcription and degradation processes via its ability to interact with SRC-3.
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RARs are also degraded by the ubiquitin-proteasome system, through the recruitment of TRIP1/SUG-1, which is a subunit of the 19S regulatory subcomplex of the proteasome with an ATPase activity.
“RARs are also degraded by the ubiquitin-proteasome system, through the recruitment of TRIP1/SUG-1, which is a subunit of the 19S regulatory subcomplex of the proteasome with an ATPase activity ( 110-112 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [112]
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- Authors
- Ferry, C., Gianni, M., Lalevée, S., Bruck, N., Plassat, J.-L., Raska, I., Garattini, E., & Rochette-Egly, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Mario Negri Institute for Pharmacological Research (IT)
- ORCID
- Garattini, Enrico
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 284
- Issue
- 12
- Pages
- 8127-8135
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2658106
- OpenAlex
- W2087685666
- Cited by
- 24
- References
- 47
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1 · 2017: 1 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-05-BLAN-0390)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SRC-3, retinoic acid receptor alpha, 19S proteasome, proteasomal degradation, transcriptional regulation, coregulator recruitment, AF-2 domain, 26S proteasome, protein-protein interaction, gene expression
- MeSH terms
- Retinoic Acid Receptor alpha, ATPases Associated with Diverse Cellular Activities, Animals, Chlorocebus aethiops, Gene Expression Regulation, HeLa Cells, Humans, Models, Biological, Transcription Factors, Transcription, Genetic, Tretinoin, Trans-Activators, Protein Structure, Tertiary, Receptors, Retinoic Acid, COS Cells, Proteasome Endopeptidase Complex, Adaptor Proteins, Signal Transducing, Histone Acetyltransferases, Nuclear Receptor Coactivator 3, LIM Domain Proteins
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