A third human retinoic acid receptor, hRAR-gamma.
Retinoic acid receptors (RARs) are retinoic acid (RA)-inducible enhancer factors belonging to the superfamily of steroid/thyroid nuclear receptors. We have previously characterized two human RAR (hRAR-alpha and hRAR-beta) cDNAs and have recently cloned their murine cognates (mRAR-alpha and mRAR-beta) together with a third RAR (mRAR-gamma) whose RNA was detected predominantly in skin, a well-known target for RA. mRAR-gamma cDNA was used here to clone its human counterpart (hRAR-gamma) from a T47D breast cancer cell cDNA library. Using a transient transfection assay in HeLa cells and a reporter gene harboring a synthetic RA responsive element, we demonstrate that hRAR-gamma cDNA indeed encodes a RA-inducible transcriptional trans-activator. Interestingly, comparisons of the amino acid sequences of all six human and mouse RARs indicate that the interspecies conservation of a given member of the RAR subfamily (either alpha, beta, or gamma) is much higher than the conservation of all three receptors within a given species. These observations indicate that RAR-alpha, -beta, and -gamma may perform specific functions. We show also that hRAR-gamma RNA is the predominant RAR RNA species in human skin, which suggests that hRAR-gamma mediates some of the retinoid effects in this tissue.
Krust
A
A
Laboratoire de Génétique Moléculaire des Eucaryotes du Centre National de la Recherche Scientifique, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Kastner
P
P
Petkovich
M
M
Zelent
A
A
Chambon
P
P
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D018168:Receptors, Retinoic Acid; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism
D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D014212:Tretinoin