scholarly journals Ligand-dependent activation of transcription in vitro by retinoic acid receptor  /retinoid X receptor   heterodimers that mimics transactivation by retinoids in vivo

1999 ◽  
Vol 96 (5) ◽  
pp. 1995-2000 ◽  
Author(s):  
F. J. Dilworth ◽  
C. Fromental-Ramain ◽  
E. Remboutsika ◽  
A. Benecke ◽  
P. Chambon
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Retinoid X Receptor ◽  
Acid Receptor ◽  
Activation Of Transcription ◽  
Transcription In Vitro

Ligand-inducible retinoid X receptor-mediated protein: DNA interactions in the retinoic acid receptor β2 gene promoter in vivo

1998 ◽  
Vol 136 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Masato Ikeda ◽  
Remco A Spanjaard ◽  
Elizabeth W Noordhoek ◽  
Akio Kawaguchi ◽  
Toshimasa Onaya ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Gene Promoter ◽  
Retinoid X Receptor ◽  
Dna Interactions ◽  
Acid Receptor ◽  
Protein Dna Interactions ◽  
Retinoic Acid Receptor Β2

scholarly journals Pharmacological Activity of Retinoic Acid Receptor Alpha-Selective Antagonists in Vitro and in Vivo

2013 ◽  
Vol 4 (5) ◽  
pp. 446-450 ◽  
Author(s):  
Sanny S. W. Chung ◽  
Rebecca A. D. Cuellar ◽  
Xiangyuan Wang ◽  
Peter R. Reczek ◽  
Gunda I. Georg ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Pharmacological Activity ◽  
Retinoic Acid Receptor ◽  
Retinoic Acid Receptor Alpha ◽  
Acid Receptor ◽  
Receptor Alpha ◽  
Selective Antagonists

scholarly journals Specific and Redundant Functions of Retinoid X Receptor/Retinoic Acid Receptor Heterodimers in Differentiation, Proliferation, and Apoptosis of F9 Embryonal Carcinoma Cells

1997 ◽  
Vol 139 (3) ◽  
pp. 735-747 ◽  
Author(s):  
Hideki Chiba ◽  
John Clifford ◽  
Daniel Metzger ◽  
Pierre Chambon
Keyword(s):  
Retinoic Acid ◽  
Embryonal Carcinoma ◽  
Retinoic Acid Receptor ◽  
Retinoid X Receptor ◽  
Carcinoma Cells ◽  
Embryonal Carcinoma Cells ◽  
Acid Receptor ◽  
Proliferation And Apoptosis ◽  
Redundant Functions

We have generated F9 murine embryonal carcinoma cells in which either the retinoid X receptor (RXR)α and retinoic acid receptor (RAR)α genes or the RXRα and RARγ genes are knocked out, and compared their phenotypes with those of wild-type (WT), RXRα−/−, RARα−/−, and RARγ−/− cells. RXRα−/−/ RARα−/− cells were resistant to retinoic acid treatment for the induction of primitive and parietal endodermal differentiation, as well as for antiproliferative and apoptotic responses, whereas they could differentiate into visceral endodermlike cells, as previously observed for RXRα−/− cells. In contrast, RXRα−/−/RARγ−/− cells were defective for all three types of differentiation, as well as antiproliferative and apoptotic responses, indicating that RXRα and RARγ represent an essential receptor pair for these responses. Taken together with results obtained by treatment of WT and mutant F9 cells with RAR isotype– and panRXR-selective retinoids, our observations support the conclusion that RXR/ RAR heterodimers are the functional units mediating the retinoid signal in vivo. Our results also indicate that the various heterodimers can exert both specific and redundant functions in differentiation, proliferation, and apoptosis. We also show that the functional redundancy exhibited between RXR isotypes and between RAR isotypes in cellular processes can be artifactually generated by gene knockouts. The present approach for multiple gene targeting should allow inactivation of any set of genes in a given cell.

scholarly journals Retinoid X receptor (RXR) within the RXR-retinoic acid receptor heterodimer binds its ligand and enhances retinoid-dependent gene expression.

1997 ◽  
Vol 17 (2) ◽  
pp. 644-655 ◽  
Author(s):  
S Minucci ◽  
M Leid ◽  
R Toyama ◽  
J P Saint-Jeannet ◽  
V J Peterson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Limited Proteolysis ◽  
Retinoid X Receptor ◽  
Acid Receptor ◽  
Synergistic Activation ◽  
P19 Embryonal Carcinoma Cells ◽  
The Stability

Retinoic acid receptor (RAR) and retinoid X receptor (RXR) form heterodimers and regulate retinoid-mediated gene expression. We studied binding of RXR- and RAR-selective ligands to the RXR-RAR heterodimer and subsequent transcription. In limited proteolysis analyses, both RXR and RAR in the heterodimer bound their respective ligands and underwent a conformational change in the presence of a retinoic acid-responsive element. In reporter analyses, the RAR ligand (but not the RXR ligand), when added singly, activated transcription, but coaddition of the two ligands led to synergistic activation of transcription. This activation required the AF-2 domain of both RXR and RAR. Genomic footprinting analysis was performed with P19 embryonal carcinoma cells, in which transcription of the RARbeta gene is induced upon retinoid addition. Paralleling the reporter activation data, only the RAR ligand induced in vivo occupancy of the RARbeta2 promoter when added singly. However, at suboptimal concentrations of RAR ligand, coaddition of the RXR ligand increased the stability of promoter occupancy. Thus, liganded RXR and RAR both participate in transcription. Finally, when these ligands were tested for teratogenic effects on zebra fish and Xenopus embryos, we found that coadministration of the RXR and RAR ligands caused more severe abnormalities in these embryos than either ligand alone, providing biological support for the synergistic action of the two ligands.

scholarly journals Retinoic acid disrupts the Golgi apparatus and increases the cytosolic routing of specific protein toxins.

1994 ◽  
Vol 125 (4) ◽  
pp. 743-753 ◽  
Author(s):  
Y N Wu ◽  
M Gadina ◽  
J H Tao-Cheng ◽  
R J Youle
Keyword(s):  
Retinoic Acid ◽  
Golgi Apparatus ◽  
Retinoic Acid Receptor ◽  
Receptor Activation ◽  
Marker Enzyme ◽  
Ricin A Chain ◽  
Acid Receptor ◽  
A Chain ◽  
Ricin A

All-trans retinoic acid can specifically increase receptor mediated intoxication of ricin A chain immunotoxins more than 10,000 times, whereas fluid phase endocytosis of ricin A chain alone or ricin A chain immunotoxins was not influenced by retinoic acid. The immunotoxin activation by retinoic acid does not require RNA or protein synthesis and is not a consequence of increased receptor binding of the immunotoxin. Vitamin D3 and thyroid hormone T3, that activate retinoic acid receptor (RAR) cognates, forming heterodimers with retinoid X receptor (RXR), do not affect the potency of immunotoxins. Among other retinoids tested, 13-cis retinoic acid, which binds neither RAR nor RXR, also increases the potency of the ricin A chain immunotoxin. Therefore, retinoic acid receptor activation does not appear to be necessary for immunotoxin activity. Retinoic acid potentiation of immunotoxins is prevented by brefeldin A (BFA) indicating that in the presence of retinoic acid, the immunotoxin is efficiently routed through the Golgi apparatus en route to the cytoplasm. Directly examining cells with a monoclonal antibody (Mab) against mannosidase II, a Golgi apparatus marker enzyme, demonstrates that the Golgi apparatus changes upon treatment with retinoic acid from a perinuclear network to a diffuse aggregate. Within 60 min after removal of retinoic acid the cell reassembles the perinuclear Golgi network indistinguishable with that of normal control cells. C6-NBD-ceramide, a vital stain for the Golgi apparatus, shows that retinoic acid prevents the fluorescent staining of the Golgi apparatus and eliminates fluorescence of C6-NBD-ceramide prestained Golgi apparatus. Electron microscopy of retinoic acid-treated cells demonstrates the specific absence of any normal looking Golgi apparatus and a perinuclear vacuolar structure very similar to that seen in monensin-treated cells. This vacuolization disappears after removal of the retinoic acid and a perinuclear Golgi stacking reappears. These results indicate that retinoic acid alters intracellular routing, probably through the Golgi apparatus, potentiating immunotoxin activity indepedently of new gene expression. Retinoic acid appears to be a new reagent to manipulate the Golgi apparatus and intracellular traffic. As retinoic acid and immunotoxins are both in clinical trials for cancer therapy, their combined activity in vivo would be interesting to examine.

scholarly journals Inhibitory effect of retinoic acid receptor agonists on in vitro chondrogenic differentiation

2019 ◽  
Vol 95 (2) ◽  
pp. 202-208
Author(s):  
Yusuke Sumitani ◽  
Kenta Uchibe ◽  
Kaya Yoshida ◽  
Yao Weng ◽  
Jiajie Guo ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Chondrogenic Differentiation ◽  
Retinoic Acid Receptor ◽  
Inhibitory Effect ◽  
Acid Receptor ◽  
Receptor Agonists

scholarly journals Effects of Vitamin-A Status on Hamster Tracheal Epithellum in Viva in Vitro

1989 ◽  
Vol 11 (3) ◽  
pp. 1-6 ◽  
Author(s):  
Luigi M. De Luca ◽  
Elizabeth M. McDowell
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Retinoic Acid Receptor ◽  
Normal Liver ◽  
Acid Receptor ◽  
New Horizons ◽  
Vitamin A Status ◽  
Essential Nutrient ◽  
Hepatoma Tissue

In this paper we have suggested the new concept of exotrophic cells, i.e. cells that have conditionally escaped the need for an essential nutrient, such as vitamin A. These exotrophs might become fixed by a mutation and eventually contribute to the tumorigenic phenotype. The discovery of the retinoic acid receptor (RAR) has opened up new horizons in the search for the mechanism of action of retinoic acid [17; 18]. It is intriguing that a second retinoic acid receptor, RARE, is abundantly expressed in hepatoma tissue and not in normal liver; Benbrook et al. [191 suggest that the erroneous expression of the RARE might contribute to tumour development in liver. How and whether these findings relate to the vitamin-A-deficient status of hepatoma cells remains to be understood.

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