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Abstract
Retinoids play an important role in development, differentiation, and homeostasis.
The discovery of retinoid receptors belonging to the superfamily of nuclear ligand-activated
transcriptional regulators has revolutionized our molecular understanding as to how
these structurally simple molecules exert their pleiotropic effects. Diversity in
the control of gene expression by retinoid signals is generated through complexity
at different levels of the signaling pathway. A major source of diversity originates
from the existence of two families of retinoid acid (RA) receptors (R), the RAR isotypes
(alpha, beta, and gamma) and the three RXR isotypes (alpha, beta, and gamma), and
their numerous isoforms, which bind as RXR/RAR heterodimers to the polymorphic cis-acting
response elements of RA target genes. The possibility of cross-modulation (cross-talk)
with cell-surface receptors signaling pathways, as well as the finding that RARs and
RXRs interact with multiple putative coactivators and/or corepressors, generates additional
levels of complexity for the array of combinatorial effects that underlie the pleiotropic
effects of retinoids. This review focuses on recent developments, particularly in
the area of structure-function relationships.