2 - Retinoic acid receptors

Summary

Introduction

The retinoids are a group of compounds that includes both natural and synthetic derivatives of retinol (vitamin A). Retinoic acid (RA), a member in this class of small lipophilic molecules, is known to exert profound effects on development and differentiation in a wide variety of systems. In the vitamin-A-deprived rat, exogenous RA is able to replace vitamin A for all its functions, with the exception of the requirement of vitamin A for vision. RA is therefore believed to act as the primary active metabolite of vitamin A in the regulation of development and homeostasis. The recent discovery of RA receptors which belong to the superfamily of steroid hormone receptors provided a model for the molecular mechanism of most, if not all, of the extravisual action of retinoids (Giguère et al., 1987; Petkovich et al., 1987). This family of nuclear receptors controls cell functions by directly regulating gene expression; by analogy, it is believed that the interaction between RA and one of its receptors may induce a cascade of regulatory events through the activation of specific gene networks by the ligand–receptor complex. This discovery not only offered the opportunity to analyze in great detail the structure, function and pattern of expression of the RA receptors, but also provided the necessary molecular tools to facilitate the identification and characterization of developmental control genes. In this review, I first give a brief overview of the numerous biological activities ascribed to natural retinoids, an exercise that emphasizes the need for the large family of RA receptors and the complex set of intracellular interactions involved in the transduction of the retinoid signal.