History of Retinoic Acid Receptors

  • Doris M. Benbrook
  • Pierre Chambon
  • Cécile Rochette-Egly
  • Mary Ann Asson-Batres
Part of the Subcellular Biochemistry book series (SCBI, volume 70)

Abstract

The discovery of retinoic acid receptors arose from research into how vitamins are essential for life. Early studies indicated that Vitamin A was metabolized into an active factor, retinoic acid (RA), which regulates RNA and protein expression in cells. Each step forward in our understanding of retinoic acid in human health was accomplished by the development and application of new technologies. Development cDNA cloning techniques and discovery of nuclear receptors for steroid hormones provided the basis for identification of two classes of retinoic acid receptors, RARs and RXRs, each of which has three isoforms, α, β and ɣ. DNA manipulation and crystallographic studies revealed that the receptors contain discrete functional domains responsible for binding to DNA, ligands and cofactors. Ligand binding was shown to induce conformational changes in the receptors that cause release of corepressors and recruitment of coactivators to create functional complexes that are bound to consensus promoter DNA sequences called retinoic acid response elements (RAREs) and that cause opening of chromatin and transcription of adjacent genes. Homologous recombination technology allowed the development of mice lacking expression of retinoic acid receptors, individually or in various combinations, which demonstrated that the receptors exhibit vital, but redundant, functions in fetal development and in vision, reproduction, and other functions required for maintenance of adult life. More recent advancements in sequencing and proteomic technologies reveal the complexity of retinoic acid receptor involvement in cellular function through regulation of gene expression and kinase activity. Future directions will require systems biology approaches to decipher how these integrated networks affect human stem cells, health, and disease.

Keywords

Retinoic Acid Glucocorticoid Receptor Nuclear Receptor Nuclear Hormone Receptor Estrogen Response Element 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ChIP

Chromatin immunoprecipitation

ChIP-seq

Chromatin immunoprecipitation coupled with deep sequencing

cDNA

Complementary DNA

CRABP

Cellular retinoic acid binding protein

CRBP

Cellular retinol binding protein

DNA

Deoxyribonucleic acid

DBD

DNA binding domain

LBD

Ligand binding domain

NMR

Nuclear magnetic resonance

RA

Retinoic acid

RAR

Retinoic acid receptor

RARE

Retinoic acid response element

RNA

Ribonucleic acid

RNA-seq

High throughput RNA sequencing

RXR

Retinoic X receptor

VAD

Vitamin A deficiency

Notes

Acknowledgments

We thank Gabriel R Batres for assistance with the design and preparation of Fig. 1.4.

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Doris M. Benbrook
    • 1
    • 2
  • Pierre Chambon
    • 3
  • Cécile Rochette-Egly
    • 3
  • Mary Ann Asson-Batres
    • 4
  1. 1.Department of Obstetrics and GynecologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Department of Pharmaceutical SciencesUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  3. 3.IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), INSERM, U964, CNRS, UMR7104Université de StrasbourgIllkirch CedexFrance
  4. 4.Department of Biological SciencesTennessee State UniversityNashvilleUSA

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