Phosphorylation by p38MAPK and recruitment of SUG‐1 are required for RA‐induced RARγ degradation and transactivation
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The nuclear retinoic acid receptor RAR gamma 2 undergoes proteasome-dependent degradation upon ligand binding. Here we provide evidence that the domains that signal proteasome-mediated degradation overlap with those that activate transcription, i.e. the activation domains AF-1 and AF-2. The AF-1 domain signals RAR gamma 2 degradation through its phosphorylation by p38MAPK in response to RA. The AF-2 domain acts via the recruitment of SUG-1, which belongs to the 19S regulatory subunit of the 26S proteasome. Blocking RAR gamma 2 degradation through inhibition of either the p38MAPK pathway or the 26S proteasome function impairs its RA-induced transactivation activity. Thus, the turnover of RAR gamma 2 is linked to transactivation.
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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 [111]
RA activates p38MAPK in fibroblasts, mouse embryo carcinoma cells, mammary breast tumor cells, and leukemia cells.
“RA activates the p38 mitogen-activated protein kinase (p38MAPK) in fi broblasts, mouse embryo carcinoma cells, mammary breast tumor cells, and leukemia cells ( 96,111,114,115 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [111]
At the end of the RA signal, the proteasomal degradation of RARγ depends on phosphorylation by p38MAPK of an additional serine residue located in the NTD.
“At the end of the RA signal, the proteasomal degradation of RAR ␥ has been shown to depend on the phosphorylation by p38MAPK of an additional serine residue located in the NTD ( 110, 111 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [111]
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Retinoic acid-mediated phospholipase A2 signaling in the nucleus
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TRIM32 promotes neural differentiation through retinoic acid receptor-mediated transcription
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Nuclear receptor superfamily: Principles of signaling
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Self-citationBruck, N., Bastien, J., Bour, G., Tarrade, A., Plassat, J.-L., Bauer, A., Adam-Stitah, S., & Rochette-Egly, C. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2004.12.006 · Cited by 52 · see citing works
Self-citationNuclear hormone receptor degradation and gene transcription: An update
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Bour, G., Plassat, J., Bauer, A., Lalevée, S., & Rochette‐Egly, C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501344200 · Cited by 50 · see citing works
Self-citationAkt phosphorylates and suppresses the transactivation of retinoic acid receptor α
Srinivas, H., Xia, D., Moore, N. L., Uray, I. P., Kim, H., Ma, L., Weigel, N. L., Brown, P. H., & Kurie, J. M. (2006) · Biochemical Journal · doi:10.1042/bj20051794 · Cited by 49 · see citing works
Lysine Trimethylation of Retinoic Acid Receptor-α
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Retinoids in hematology: a timely revival?
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Phytochemical Regulation of UDP-Glucuronosyltransferases: Implications for Cancer Prevention
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Nuclear and extranuclear effects of vitamin A
Iskakova, M., Karbyshev, M. S., Piskunov, A., & Rochette‐Egly, C. (2015) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2014-0522 · Cited by 44 · see citing works
Self-citationRoles for APIS and the 20S proteasome in adenovirus E1A‐dependent transcription
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Phosphorylation of Steroidogenic Factor 1 Is Mediated by Cyclin-Dependent Kinase 7
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Gianni’, M., Couturier‐Tarrade, A., Nigro, E. A., Garattini, E., & Rochette‐Egly, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304952200 · Cited by 44 · see citing works
Self-citationCross Talk between Retinoic Acid Signaling and Transcription Factor GATA-2
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Implication of the Ubiquitin/Proteasome System in Myc-Regulated Transcription
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A role for IRF3-dependent RXRα repression in hepatotoxicity associated with viral infections
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Different ways to regulate the PPARα stability
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Self-citationRetinoids in the Pathogenesis and Treatment of Liver Diseases
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CDK1 interacts with RARγ and plays an important role in treatment response of acute myeloid leukemia
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Nuclear and Extra-Nuclear Effects of Retinoid Acid Receptors: How They Are Interconnected
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A Unique Cytoplasmic Localization of Retinoic Acid Receptor-γ and Its Regulations
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The potential of retinoids for combination therapy of lung cancer: Updates and future directions
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The Ski protein negatively regulates Siah2-mediated HDAC3 degradation
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HACE1: A novel repressor of RAR transcriptional activity
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Rétinoïdes : mécanismes d’action
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Nuclear GRP75 Binds Retinoic Acid Receptors to Promote Neuronal Differentiation of Neuroblastoma
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Regulation of Peroxisome Proliferator–Activated Receptor-α by MDM2
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Self-citationModulation of Retinoic Acid Receptor Alpha Activity by Lysine Methylation in the DNA Binding Domain
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Self-citationGenaro, P. D., Simón, M. V., Rotstein, N. P., & Politi, L. E. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-11049 · Cited by 25 · see citing works
- Authors
- Giannì, M., Bauer, A., Garattini, E., Chambon, P., & Rochette‐Egly, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Mario Negri Institute for Pharmacological Research (IT)
- Corresponding author
- Rochette‐Egly, Cécile
- Venue
- The EMBO Journal
- Published
- 2002-07-15
- Volume
- 21
- Issue
- 14
- Pages
- 3760-3769
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC126119
- OpenAlex
- W2004745065
- Cited by
- 151
- References
- 58
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2019: 7 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 2
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Association pour la Recherche sur le Cancer
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Fondazione Italiana per la Ricerca sul Cancro
- 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 › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- retinoic acid receptor gamma, p38 MAPK, proteasomal degradation, 26S proteasome, protein phosphorylation, receptor turnover
- MeSH terms
- ATPases Associated with Diverse Cellular Activities, Retinoic Acid Receptor gamma, Animals, Carrier Proteins, Cysteine Endopeptidases, Ligands, Multienzyme Complexes, Phosphorylation, Transcription Factors, Tretinoin, Transcriptional Activation, Receptors, Retinoic Acid, COS Cells, Mitogen-Activated Protein Kinases, Ubiquitin, Proteasome Endopeptidase Complex, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, LIM Domain Proteins
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