Characterization of three RXR genes that mediate the action of 9-cis retinoic acid

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 -