Retinoic acid receptor complexes

The hormone-receptor complexes interact pairwise with DNA. These pairs (dimers) may consist of two identical hormone-receptor complexes (homodimeric form, e.g., with adrenal or gonadal hormones). The thyroid hormone-receptor complex occurs in heterodimeric form and combines with a cis-retinoic acid-receptor complex. 

Wolf G. 2000. Cellular retinoic acid binding protein II a coactivator of the transactivation by the retinoic acid receptor complex RAR, RXR. Nutr. Rev. 58 151-53... 

CPR can be used to find continuous paths for complex transitions that might have hundreds of saddle points and need to be described by thousands of path points. Examples of such transitions include the quaternary transition between the R and T states of hemoglobin [57] and the reorganization of the retinoic acid receptor upon substrate entry [58]. Because CPR yields the exact saddle points as part of the path, it can also be used in conjunction with nonnal mode analysis to estimate the vibrational entropy of activation... 

ASBT has a complex regulatory system reflecting the importance of this transporter to bile-acid pool size and bile-acid synthesis rates. Hepatic nuclear factor la (HNF-la) is necessary for expression of ASBT as knockout mice showed no expression and had defective bile-acid transport.Conversely, FXR-null mice showed no difference in expression of ASBT, showing that FXR plays no part in regulation of ASBT. In man, HNF-la controls baseline promoter activity of the ASBT gene as the minimal construct with full promoter activity was found to have 3 HNF-la binding sites. These authors also showed that the promoter construct bound peroxisome proliferator activated receptor a (PPARa)/9 cis retinoic acid receptor heterodimer, demonstrating a link between bile-acid absorption and hepatic lipid metabolism mediated by PPARa. 

The PPAR-RXR complex binds to specific DNA response elements (PPREs composed of two hexanucleotide direct repeats) in gene promoters and functions as a transcription factor, which can be activated by either RXR- or PPAR-specific ligands. The consensus site for PPAR-RXR binding is a direct repeat of two -AGGTCA- sequences with a single nucleotide spacer (a DR1 response element). However, DR1 elements may also bind other complexes, including RAR (retinoic acid receptor)/RXR heterodimers and RXR homodimers (25). Further specificity for binding of PPARs may be provided by sequences that flank the DR1 site (26). 

Tissues contain two types of receptors for 1,25-dihydroxyvitamin D a classic steroid hormone nuclear receptor and a putative membrane receptor. 1,25-Dihydroxyvitamin D interacts with the nuclear receptor to form a receptor-ligand complex (Fig. 30-4). This complex then interacts with other nuclear proteins, such as the retinoic acid receptor (RXR) to form a functional transcription complex. The main effect of this transcription complex is to alter the amount of mRNAs coding for selected proteins such as cal-bindin, the calcium transport protein in the intestine, and the vitamin D receptor. In concert with PTH, 1,25-dihydroxyvitamin D acts to mobilize calcium from bone.As a consequence, serum calcium and phosphate homeostasis is maintained by a combination of 1,25-dihydroxyvitamin D stimulation of intestinal absorption and bone turnover. 

G10. Giguere, V., Retinoic acid receptors and cellular retinoid binding proteins Complex interplay in retinoic signalling. Endocr. Rev. 15, 61-79 (1994). 

Tretinoin is a synthetic (all trans) retinoic acid. Retinol and retinaldehyde are also converted into retinoic acid in the target cell where it participates in metabolic activity. The retinoic acid penetrates the cell s nucleus, where it binds with a retinoic acid receptor (RAR). The complex formed by the retinoic acid and the RAR (RA-RAR) interferes with certain areas of DNA by modulating the expression of some genes. It appears that retinoic acid alters the regulation of the cell cycle. ... 

Sun, G., Porter, W. and Safe, S. (1998) Estrogen-induced retinoic acid receptor a 1 gene expression role of estrogen receptor—Spl complex. Molecular Endocrinology, 12, 882—890. 

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