Physical and Functional Interactions between Cellular Retinoic Acid Binding Protein II and the Retinoic Acid-Dependent Nuclear Complex
Open accessAbstract
Two sorts of proteins bind to, and mediate the developmental and homeostatic effects of, retinoic acid (RA): the RAR and RXR nuclear receptors, which act as ligand-dependent transcriptional regulators, and the cellular RA binding proteins (CRABPI and CRABPII). CRABPs are generally known to be implicated in the synthesis, degradation, and control of steady-state levels of RA, yet previous and recent data have indicated that they could play a role in the control of gene expression. Here we show for the first time that, both in vitro and in vivo, CRABPII is associated with RARalpha and RXRalpha in a ligand-independent manner in mammalian cells (HL-60, NB-4, and MCF-7). In the nucleus, this protein complex binds the RXR-RAR-specific response element of an RA target gene (RARE-DR5). Moreover, in the presence of retinoids that bind both the nuclear receptors and CRABPII, enhancement of transactivation by RXRalpha-RARalpha heterodimers is observed in the presence of CRABPII. Thus, CRABPII appears to be a novel transcriptional regulator involved in RA signaling.
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CRABPII significantly enhances the transcriptional activity of RARs and sensitizes the cells to RA biological activities.
“It was demonstrated that by directly delivering RA to RARs, CRABPII significantly enhances the transcriptional activity of RARs and sensitizes the cells to RA biological activities.”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [18]
Upon binding of RA, CRABPII mobilizes to the nucleus, where it associates with RARs through direct protein-protein interactions.
“Upon binding of RA, CRABPII mobilizes to the nucleus, where it associates with RARs through direct protein-protein interactions (17)(18)(19).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [18]
CRABPII specifically associates with RA with subnanomolar affinities.
“It is a small cytosolic protein, which specifi cally associates with RA with subnanomolar affi nities.”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [18]
In the cytosol, RA binds CRABPII, which belongs to the intracellular lipid binding protein (iLBP) family.
“In the cytosol, RA is well known to bind the cellular retinoic acid-binding protein CRABPII, which belongs to the intracellular lipid binding proteins iLBP family.”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [18]
The resulting complex channels RA from the binding protein to the RAR and markedly facilitates the formation of the liganded receptor.
“The resulting complex channels RA from the binding protein to the RAR and markedly facilitates the formation of the liganded receptor.”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [18]
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“The nuclear receptors belong to the steroid/ thyroid hormone superfamily, members of which act as liganddependent transcription factors (9, 34).”
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Self-citationThe acetyltransferase activity of CBP stimulates transcription
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- Authors
- Delva, L., Bastie, J.-N., Rochette-Egly, C., Kraïba, R., Balitrand, N., Despouy, G., Chambon, P., & Chomienne, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, 67404 Illkirch Cedex, CU de Strasbourg, France
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1999-10-01
- Volume
- 19
- Issue
- 10
- Pages
- 7158-7167
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC84709
- OpenAlex
- W2132335701
- Cited by
- 208
- References
- 5
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 8 · 2018: 8 · 2017: 2 · 2016: 9 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 8
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- 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
- CRABP2, retinoic acid, retinoic acid receptor alpha, retinoid X receptor alpha, RAR/RXR heterodimers, retinoic acid response element, DR5, transcriptional regulation, retinoid signaling, HL-60 cells, MCF-7 cells
- MeSH terms
- Bone Marrow Cells, Breast Neoplasms, Humans, Nuclear Proteins, Protein Binding, Transcription Factors, Tumor Cells, Cultured, Signal Transduction, Transcriptional Activation, Receptors, Retinoic Acid, Teratocarcinoma, HL-60 Cells, Response Elements, Retinoid X Receptors
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