Phosphorylation of activation functions AF‐1 and AF‐2 of RARα and RARγ is indispensable for differentiation of F9 cells upon retinoic acid and cAMP treatment
Open accessAbstract
The role of RAR alpha 1 and RAR gamma 2 AF-1 and AF-2 activation functions and of their phosphorylation was investigated during RA-induced primitive and parietal differentiation of F9 cells. We found that: (i) primitive endodermal differentiation requires RAR gamma 2, whereas parietal endodermal differentiation requires both RAR gamma 2 and RAR alpha 1, and in all cases AF-1 and AF-2 must synergize; (ii) primitive endodermal differentiation requires the proline-directed kinase site of RAR gamma 2-AF-1, whereas parietal endodermal differentiation additionally requires that of RAR alpha 1-AF-1; (iii) the cAMP-induced parietal endodermal differentiation also requires the protein kinase A site of RAR alpha-AF-2, but not that of RAR gamma; and (iv) the AF-1-AF-2 synergism and AF-1 phosphorylation site requirements for RA-responsive gene induction are promoter context-dependent. Thus, AF-1 and AF-2 of distinct RARs exert specific cellular and molecular functions in a cell-autonomous system mimicking physiological situations, and their phosphorylation by kinases belonging to two main signalling pathways is required to enable RARs to transduce the RA signal during F9 cell differentiation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The differentiation of F9 cells in primitive endoderm involves the RARγ2 subtype.
“Invalidation experiments from our laboratory revealed that the differentiation of F9 cells in primitive endoderm ( 139 ) and that of ES cells into neurons (Al Tanoury et al., unpublished observations) involves the RAR ␥ 2 subtype.”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [139]
Cites
A decade of molecular biology of retinoic acid receptors
Chambon, P. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.9.8801176 · Cited by 2,889 · cited 5× · see citing works
“For differentiation studies, 105 cells were cultured in a 10 cm dish, and treated with retinoids alone or in combination with cAMP for 96 h and 120 h, with a change of media after 48 h. Retinoids (T-RA, BMS753, BMS961, BMS614 and BMS649) were dissolved in ethanol and used at concentrations indicated in the figure lege…”
MethodInfluentialSelf-citationMultiplicity generates diversity in the retinoic acid signalling pathways
Leid, M., Kastner, P., & Chambon, P. (1992) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(92)90014-z · Cited by 821 · see citing works
Self-citationRochette-Egly, C., Adam, S., Rossignol, M., Egly, J.-M., & Chambon, P. (1997) · Cell · doi:10.1016/s0092-8674(00)80317-7 · Cited by 308 · see citing works
Self-citationPhosphorylation of the retinoic acid receptor-alpha by protein kinase A
Rochette-Egly, C. (1995) · Molecular Endocrinology · doi:10.1210/me.9.7.860 · Cited by 124 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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
Al Tanoury, Z., Piskunov, A., & Rochette-Egly, C. (2013) · Journal of Lipid Research · doi:10.1194/jlr.r030833 · Cited by 408 · see citing works
Self-citationNuclear receptors: integration of multiple signalling pathways through phosphorylation
Rochette-Egly, C. (2003) · Cellular Signalling · doi:10.1016/s0898-6568(02)00115-8 · Cited by 291 · see citing works
Self-citationThe nuclear receptor superfamily: a personal retrospect on the first two decades
Chambon, P. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0125 · Cited by 194 · see citing works
Self-citationKopf, E., Plassat, J.-L., Vivat, V., de Thé, H., Chambon, P., & Rochette-Egly, C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002840200 · Cited by 155 · see citing works
Self-citationGiannì, M., Bauer, A., Garattini, E., Chambon, P., & Rochette‐Egly, C. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf374 · Cited by 151 · see citing works
Self-citationA coordinated phosphorylation cascade initiated by p38MAPK/MSK1 directs RARα to target promoters
Bruck, N., Vitoux, D., Ferry, C., Duong, V., Bauer, A., de Thé, H., & Rochette‐Egly, C. (2009) · The EMBO Journal · doi:10.1038/emboj.2008.256 · Cited by 108 · see citing works
Self-citationNuclear receptor superfamily: Principles of signaling
Germain, P., Altucci, L., Bourguet, W., Rochette-Egly, C., & Gronemeyer, H. (2003) · Pure and Applied Chemistry · doi:10.1351/pac200375111619 · Cited by 53 · see citing works
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-citationLalevee, S., Bour, G., Quinternet, M., Samarut, E., Kessler, P., Vitorino, M., Bruck, N., Delsuc, M., Vonesch, J., Kieffer, B., et al. (2010) · The FASEB Journal · doi:10.1096/fj.10-160572 · Cited by 32 · see citing works
Self-citation
- Authors
- Taneja, R., Rochette‐Egly, C., Plassat, J., Penna, L., Gaub, M., & Chambon, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Chambon, Pierre
- Venue
- The EMBO Journal
- Published
- 1997-11-01
- Volume
- 16
- Issue
- 21
- Pages
- 6452-6465
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170251
- OpenAlex
- W2137553196
- Cited by
- 113
- References
- 4
- Citations by year
- 2026: 1 · 2025: 1 · 2021: 1 · 2020: 1 · 2015: 3 · 2014: 2 · 2013: 4
- FWCI
- 3.09
- 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)
- Funders
- Bristol-Myers Squibb
- Centre National de la Recherche Scientifique
- 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 alpha, retinoic acid receptor gamma, activation functions, AF-2, protein phosphorylation, F9 cells, primitive endoderm differentiation, parietal endoderm differentiation, retinoic acid signaling, cAMP signaling, protein kinase A, proline-directed kinases, transcriptional activation
- MeSH terms
- Retinoic Acid Receptor alpha, Retinoic Acid Receptor gamma, Cyclic AMP, Animals, Binding Sites, Cell Differentiation, Endoderm, Ligands, Phosphorylation, Tretinoin, Tumor Cells, Cultured, Cyclic AMP-Dependent Protein Kinases, Receptors, Retinoic Acid, Carcinoma, Embryonal, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
