Characterization of three RXR genes that mediate the action of 9-cis retinoic acid
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Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. / Mangelsdorf, D J; Borgmeyer, U; Heyman, R A; Zhou, J Y; Ong, E S; Oro, A E; Kakizuka, A; Evans, R M.
in: GENE DEV, Jahrgang 6, Nr. 3, 03.1992, S. 329-44.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Characterization of three RXR genes that mediate the action of 9-cis retinoic acid
AU - Mangelsdorf, D J
AU - Borgmeyer, U
AU - Heyman, R A
AU - Zhou, J Y
AU - Ong, E S
AU - Oro, A E
AU - Kakizuka, A
AU - Evans, R M
PY - 1992/3
Y1 - 1992/3
N2 - An understanding of the differences and similarities of the retinoid X receptor (RXR) and retinoic acid receptor (RAR) systems requires knowledge of the diversity of their family members, their patterns of expression, and their pharmacological response to ligands. In this paper we report the isolation of a family of mouse RXR genes encoding three distinct receptors (RXR alpha, beta, and gamma). They are closely related to each other in their DNA- and ligand-binding domains but are quite divergent from the RAR subfamily in both structure and ligand specificity. Recently, we demonstrated that all-trans retinoic acid (RA) serves as a "pro-hormone" to the isomer 9-cis RA, which is a high-affinity ligand for the human RXR alpha. We extend those findings to show that 9-cis RA is also "retinoid X" for mouse RXR alpha, beta, and gamma. Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA. Northern blot and in situ hybridization analyses define a broad spectrum of expression for the RXRs, which display unique patterns and only partially overlap themselves and the RARs. This study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology.
AB - An understanding of the differences and similarities of the retinoid X receptor (RXR) and retinoic acid receptor (RAR) systems requires knowledge of the diversity of their family members, their patterns of expression, and their pharmacological response to ligands. In this paper we report the isolation of a family of mouse RXR genes encoding three distinct receptors (RXR alpha, beta, and gamma). They are closely related to each other in their DNA- and ligand-binding domains but are quite divergent from the RAR subfamily in both structure and ligand specificity. Recently, we demonstrated that all-trans retinoic acid (RA) serves as a "pro-hormone" to the isomer 9-cis RA, which is a high-affinity ligand for the human RXR alpha. We extend those findings to show that 9-cis RA is also "retinoid X" for mouse RXR alpha, beta, and gamma. Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA. Northern blot and in situ hybridization analyses define a broad spectrum of expression for the RXRs, which display unique patterns and only partially overlap themselves and the RARs. This study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology.
KW - Amino Acid Sequence
KW - Animals
KW - Base Sequence
KW - Blotting, Northern
KW - Carrier Proteins
KW - Cloning, Molecular
KW - DNA
KW - Embryo, Mammalian
KW - Mice
KW - Molecular Sequence Data
KW - Nuclear Proteins
KW - Nucleic Acid Hybridization
KW - Plasmids
KW - RNA, Messenger
KW - Receptors, Cell Surface
KW - Receptors, Retinoic Acid
KW - Retinoid X Receptors
KW - Sequence Homology, Nucleic Acid
KW - Substrate Specificity
KW - Transcription Factors
KW - Transcription, Genetic
KW - Transcriptional Activation
KW - Transfection
KW - Tretinoin
M3 - SCORING: Journal article
C2 - 1312497
VL - 6
SP - 329
EP - 344
JO - GENE DEV
JF - GENE DEV
SN - 0890-9369
IS - 3
ER -