Critical Reviews in Oral Biology & Medicine, Vol 6, 284-301, Copyright © 1995 by International & American Associations for Dental Research
Retinoid receptors and keratinocytes
C. Fisher, M. Blumenberg and M. Tomic-Canic
Department of Biology, Vassar College, New York, NY, USA.
In 1987, a tremendous boost in our understanding of the action of dietary
vitamin A occurred with the discovery and characterization of nuclear
receptors for retinoic acid, the active form of the vitamin, in the
laboratories of P. Chambon and R. Evans. They have shown that the nuclear
receptors are ligand-activated transcription factors capable of specific
gene regulation. Since that discovery, it has been determined that there
are at least six retinoic acid receptors belonging to two families, RARs
and RXRs, that they are differentially expressed in various mammalian
tissues, and that they act as homo- and heterodimers interacting with other
ligand-activated nuclear receptors. The domain structure of the receptors
has been described, and their DNA-binding, ligand-binding, dimerization,
and transcriptional activation regions characterized. Among the most
important retinoid-regulated genes are the homeobox proteins, regulatory
transcription factors which are responsible for body axis formation,
patterning, limb formation, and other crucial processes during development.
Retinoic acid and its receptors also regulate many differentiation markers
which are particularly important in stratified epithelia, such as skin and
oral epithelia. Our increased understanding led to improved therapy of a
large number of skin disorders, ranging from acne to wrinkles and including
epidermal and oral carcinomas.
