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A third human retinoic acid receptor, hRAR-gamma.
A Krust1, P Kastner, M Petkovich
1Laboratoire de Génétique Moléculaire des Eucaryotes du Centre National de la Recherche Scientifique, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Summary
Researchers identified and cloned the human retinoic acid receptor gamma (hRAR-gamma) gene. This receptor is crucial for mediating retinoid effects, particularly in human skin, suggesting distinct functions for different retinoic acid receptors.
Area of Science:
- Molecular Biology
- Genetics
- Endocrinology
Background:
- Retinoic acid receptors (RARs) are key nuclear receptors regulating gene expression in response to retinoic acid (RA).
- Previous studies characterized human RAR-alpha and RAR-beta, and their mouse counterparts, along with a mouse RAR-gamma predominantly found in skin.
Purpose of the Study:
- To clone the human counterpart of mRAR-gamma (hRAR-gamma) and functionally characterize its role in retinoic acid signaling.
- To investigate the evolutionary conservation and potential functional specificity of different RAR subtypes.
Main Methods:
- Cloning of hRAR-gamma cDNA from a T47D breast cancer cell library.
- Transient transfection assays in HeLa cells using a reporter gene with a synthetic RA-responsive element.
- Comparative analysis of amino acid sequences across different RAR subtypes and species.
Main Results:
- hRAR-gamma cDNA was successfully cloned and demonstrated to encode a RA-inducible transcriptional trans-activator.
- Interspecies conservation of RAR subtypes (alpha, beta, gamma) is higher than conservation within a species, suggesting specialized roles.
- hRAR-gamma RNA is the predominant RAR RNA species in human skin.
Conclusions:
- hRAR-gamma plays a significant role in mediating retinoid effects in human skin.
- The distinct conservation patterns of RAR subtypes support their specialized functions in cellular processes.