All-trans retinoic acid is a ligand for the orphan nuclear receptor RORβ

@article{StehlinGaon2003AlltransRA,
  title={All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR$\beta$},
  author={Catherine Stehlin-Gaon and Dominica Willmann and Denis Zeyer and Sarah Sanglier and Alain Van Dorsselaer and Jean-Paul Renaud and Dino Moras and Roland Sch{\"u}le},
  journal={Nature Structural Biology},
  year={2003},
  volume={10},
  pages={820-825}
}
Retinoids regulate gene expression through binding to the nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In contrast, no ligands for the retinoic acid receptor–related orphan receptors β and γ (RORβ and γ) have been identified, yet structural data and structure-function analyses indicate that RORβ is a ligand-regulated nuclear receptor. Using nondenaturing mass spectrometry and scintillation proximity assays we found that all-trans retinoic acid (ATRA) and several… 
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143 Citations

Modulation of Retinoic Acid Receptor-related Orphan Receptor α and γ Activity by 7-Oxygenated Sterol Ligands*
TLDR
It is demonstrated that 7-oxygenated sterols function as high affinity ligands for both RORα and RORγ by directly binding to their ligand-binding domains, modulating coactivator binding, and suppressing the transcriptional activity of the receptors.
Synthetic modulators of the retinoic acid receptor-related orphan receptors
TLDR
The identification of potent and selective ROR ligands will allow for a better understanding of the roles of the ROR receptors in human disease, and potentially pave the way for development of novel therapeutics.
Nuclear and extra-nuclear effects of retinoid acid receptors: how they are interconnected.
TLDR
The phosphorylation Phosphorylation state of the RARs dictates whether the transcriptional programs which are known to be induced by RA are facilitated and/or switched on, and kinase signaling pathways appear to be crucial for fine-tuning the appropriate physiological activity of R ARs.
Structures and regulation of non-X orphan nuclear receptors: A retinoid hypothesis
Monitoring ligand-mediated nuclear receptor-coregulator interactions by noncovalent mass spectrometry.
TLDR
It is shown that ESI-MS is a powerful technique that complements classical methods and allows one to obtain direct evidence for the formation of noncovalent NR complexes and determine ligand binding stoichiometries and monitor ligand effects on these complexes.
Development of novel silicon-containing inverse agonists of retinoic acid receptor-related orphan receptors.
Ligand regulation of retinoic acid receptor-related orphan receptors: implications for development of novel therapeutics
TLDR
Identification of ligands for the RORs, both endogenous and synthetic, has established these receptors as attractive new therapeutic targets for the treatment of ROR-related diseases.
Development and validation of a cell-based assay for the nuclear receptor retinoid-related orphan receptor gamma.
TLDR
A cellular assay for screening for RORγ inverse agonists is developed and demonstrated its robustness and usefulness in high-throughput screening and follow-up studies for this emerging drug target.
Understanding nuclear receptor form and function using structural biology.
TLDR
Crystal structures of the peroxisome proliferator-activated receptor-γ-retinoid X receptor α (PPARγ-RXRα) heterodimer and hepatocyte nuclear factor (HNF)-4α homodimer have recently revealed the higher order organizations of these receptor complexes on DNA, as well as the complexity and uniqueness of their domain-domain interfaces.
Selective LXXLL peptides antagonize transcriptional activation by the retinoid-related orphan receptor RORgamma.
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