Mechanisms of transactivation by retinoic acid receptors

✍ Scribed by Hendrik G. Stunnenberg

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 836 KB
• Volume: 15
• Category: Article
• ISSN: 0265-9247
• DOI: 10.1002/bies.950150504

✦ Synopsis

Abstract

Retinoids play an important role in development and differentiation^(1,2)^. Their effect is mediated through nuclear receptors, RAR (α, β and γ) and RXR (α, β and γ),Abbreviations. RAR: retinoic acid receptor; RXR: retinoid X receptor; T~3~:thyroid hormone receptor; VD~3~R: vitamin D3 receptor; PPAR: peroxisome proliferator activated receptor; EcR ecdycsone receptor; USP, ultraspiracle; NGFI‐B: also referred to as nur77a; ELP: embryonal long terminal repeat‐binding protein; FTZ‐F1: positive regulator of the fushi tarazu gene in blastodermstage embryos of Drosophila melanogaster; GR: glucocorticoid receptor; ER: estrogen receptor; RARE, retinoic acid response element; PR: progesterone receptor; DR+x: direct repeat with a spacing of x nucleotides; DBD: DNA‐binding domain; CRABP I and II: cellular retinoic acid binding protein type I and II, respectively; MoMLV: Moloney Murine Leukemia Virus; TBP: TATA‐binding protein; TAF: TBP associated factor.

which are members of a distinct subclass (hereafter referred to as type II) of the nuclear receptor superfamily that includes the thyroid hormone receptor (T~3~R), the vitamin D~3~ receptor (VD~3~R) and the peroxisome proliferator activated receptor (PPAR). Type II receptors transactivate through binding sites composed of closely related half‐sites (consensus sequence AG^G^/~T~ TCA) 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.