Vinexinβ, an atypical “sensor” of retinoic acid receptor γ signaling: union and sequestration, separation, and phosphorylation
Abstract
The transcriptional activity of nuclear retinoic acid receptors (RARs) relies on the association/dissociation of coregulators at the ligand‐binding domain. However, we determined that the N‐terminal domain (NTD) also plays a role through its phosphorylation, and we isolated vinexinβ, a cytoskeleton protein with three SH3 domains, as a new partner of the RARγ NTD. Here we deciphered the mechanism of the interaction and its role in RARY‐mediated transcription. By combining molecular and biophysical (surface plasmon resonance, NMR, and fluorescence resonance energy transfer) approaches, we demonstrated that the third SH3 domain of vinexinβ interacts with a proline‐rich domain (PRD) located in RARγ NTD and that phosphorylation at a serine located in the PRD abrogates the interaction. The affinity of the interaction was also evaluated. In vivo , vinexinβ represses RARγ‐mediated transcription and we dissected the underlying mechanism in chromatin immunoprecipitation experiments performed with F9 cells expressing RARγ wild type or mutated at the phosphorylation site. In the absence of retinoic acid (RA), vinexinβ does not occupy RARγ target gene promoters and sequesters non‐phosphorylated RARγ out of promoters. In response to RA, RARγ becomes phosphorylated and dissociates from vinexinγ. This separation allows RARγ to occupy promoters. This is the first report of an RAR corepressor association/dissociation out of promoters and regulated by phosphorylation.—Lalevée, S., Bour, G., Quinternet, M., Samarut, E., Kessler, P., Vitorino, M., Bruck, N., Delsuc, M.‐A., Vonesch, J.‐L., Kieffer, B., Rochette‐Egly, C. Vinexinβ, an atypical “sensor” of retinoic acid receptor γ signaling: union and sequestration, separation, and phosphorylation. FASEB J . 24, 4523–4534 (2010). www.fasebj.org
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When nonphosphorylated, the PRM of the RARγ subtype interacts with vinexinβ, an adaptor protein with SH3 domains.
“Recently our laboratory showed that when nonphosphorylated, the PRM of the RAR ␥ subtype interacts with vinexinß, an adaptor protein with SH3 domains.”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [75]
Vinexinβ represses RARγ-mediated transcription via inhibiting the binding of the receptor to DNA and its sequestration out of chromatin.
“As such, vinexinß represses RAR ␥ -mediated transcription via inhibiting the binding of the receptor to DNA and its sequestration out of chromatin ( 75 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [75]
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Self-citation
- Authors
- Lalevee, S., Bour, G., Quinternet, M., Samarut, E., Kessler, P., Vitorino, M., Bruck, N., Delsuc, M., Vonesch, J., Kieffer, B., & Rochette‐Egly, C.
- Affiliations
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) Institut National de la Santé et de la Recherche Médicale (INSERM), U596 Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 7104 Université de Strasbourg Illkirch France
- Centre National de la Recherche Scientifique (FR)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2010-07-15
- Volume
- 24
- Issue
- 11
- Pages
- 4523-4534
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2150963738
- Cited by
- 32
- References
- 33
- Citations by year
- 2021: 7 · 2019: 1 · 2018: 1 · 2017: 2 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Institut National de la Santé et de la Recherche Médicale
- Agence Nationale de la Recherche (ANR‐05‐BLAN‐0390‐02, ANR‐09‐BLAN‐0297‐01)
- Association pour la Recherche sur le Cancer (ARC‐07‐1‐3169)
- Fondation de l'Avenir pour la Recherche Médicale Appliquée (DEQ 20090515423)
- Institut National Du Cancer (INCa‐PL06‐095, PL07‐96099)
- Ministry of Advanced Education and Skills Development
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- retinoic acid receptor gamma, SH3 domain, proline-rich region, protein phosphorylation, transcriptional repression, retinoic acid signaling, ligand-binding domain, promoter binding
- MeSH terms
- Retinoic Acid Receptor gamma, Amino Acid Sequence, Animals, Chlorocebus aethiops, Molecular Sequence Data, Mutation, Phosphorylation, Promoter Regions, Genetic, Protein Binding, Recombinant Proteins, Signal Transduction, Receptors, Retinoic Acid, COS Cells, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice
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