Mechanisms of transactivation by retinoic acid receptors

Retinoids play an important role in development and differentiation. Their effect is mediated through nuclear receptors, RAR (alpha, beta and gamma) and RXR (alpha, beta and gamma), which are members of a distinct subclass (hereafter referred to as type II) of the nuclear receptor superfamily that includes the thyroid hormone receptor (T3R), the vitamin D3 receptor (VD3R) and the peroxisome proliferator activated receptor (PPAR). Type II receptors transactivate through binding sites composed of closely related half-sites (consensus sequence AGG/TTCA) arranged as direct repeats and, with the possible exception of RXR, do not bind to their cognate binding sites as homodimers but require RXR for high affinity binding. RXR thus provides a link between biologically distinct ligand induced pathways and is a potential target for cross-regulation. In addition, RAR can utilize alternative routes to enhance transcription initiation mediated through transcriptional co-activators which are expressed in a cell-type specific manner.