Retinoid receptors ligand-receptor interaction

CRABP (1) and CRABP (11) function to transport retinoic acid into the nucleus for binding to retinoid receptors. CRABP(ll), with retinoic acid bound, also interacts directly with the liganded RAR-RXR heterodimer bound to hormone response elements on DNA and enhances the activity of the nuclear receptor (Section2.3.2.1 Delvaetal., 1999). 

Wei LN, Farooqui M, Hu XL. 2001. Ligand-dependent formation of retinoid receptors, receptor interacting protein 140 and histone deacetylase complex is mediated by a novel receptor interacting motif of RIP140. J. Biol. Chem. 276 16107-12... 

Nuclear hormone receptors (NRs) are ligand-activated transcription factors that regulate gene expression by interacting with hormone response elements on target genes (see also Chapter 12). This occurs via the formation of monomers, homodimers, or heterodimers generally with the retinoid X receptor (RXR) and interaction with the hormone response element [83,84],... 

Retinoids (derivatives of retinol) act like steroid hormones and interact with specific receptor proteins in the cell nucleus. The ligand-receptor complexes bind to specific DNA sequences, where they control the transcription of particular genes. 

The ligands for several of the nuclear receptors, including VDR and retinoid receptors, are known to play a role in heterodimer interactions (2,23) as well as in the interaction of these receptors with other transcription factors (6,7,24). The two-hybrid system is well-suited to test the ligand dependence of nuclear receptor interactions with other proteins. 

The receptor protein (52 kDa) is a member of the steroid hormone receptor superfamily, which has a DNA-binding as well as ligand-binding domain. Another receptor, the retinoid X receptor is also involved, and after binding of the peroxisome proliferator, the two receptors form a heterodimer. This binds to a regulatory DNA sequence known as the peroxisome proliferator response element. The end result of the interaction between peroxisome proliferators and this system is that genes are switched on, leading to increases in synthesis (induction) of both microsomal and peroxisomal enzymes and possibly hyperplasia. 

Like other nuclear receptors (e.g., steroid hormone receptors, thyroid hormone receptors) the PPARs function as ligand-activated transcription factors. As illustrated in Fig. 1 (see color insert) individual PPARs function as dimers with members of the retinoid X receptor (RXR) family (23). Evidence for an interaction of PPARs with RXRs includes co-expression studies that were performed with yeast lacking endogenous nuclear receptors (24). 

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