Retinoic acid receptor regulation

Thyroid hormone, 1,25-dihydroxy vitamin D, and retinoic acid receptor regulation of transcription. The hormone receptor (HR) is dimerized at site (3) and is bound to DNA at hormone response element site (2). Without the ligand, transcription is inactive due to the interaction of HR with corepressor at site 4. When the ligand (hormone) binds to HR, the bound corepressor dissociates leading to an interaction between the coactivator and HR. These regulatory changes result in increased transcription. 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

Lian, E, K. Q. Hu, R. M. Russell, and X. D. Wang. 2006. Beta-cryptoxanthin suppresses the growth of immortalized human bronchial epithelial cells and non-small-cell lung cancer cells and up-regulates retinoic acid receptor beta expression. Int J Cancer 119(9) 2084—2089. 

The mechanisms of corticosteroid receptor regulation of transcription have been elucidated. Both type I and type II corticosteroid receptors are members of a superfamily of ligand-activated transcription factors defined by protein sequence similarity. Included in this superfamily are various other steroid receptors, such as the estrogen receptor, as well as members of the retinoic acid receptor... 

Agarwal C, Chandraratna RAS, Teng M, Nagpal S, Rorke EA, and Eckert RL [1996] Differential regulation of human ectocervical epithelial cell line proliferation and differentiation by retinoid x receptor- and retinoic acid receptor-specific retinoids. Cell Growth Differentiation 7 521-530... 

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. 

Retinoid action depends on binding to both cytosolic and nuclear retinoic acid receptors (RARs). RARs have distinct DNA and retinoid-binding domains, and they function as pairs and bind to the retinoic acid receptor element (RARE) to regulate transcriptional activity. 

Figure 29-6. Gene transcription is regulated by retinoic acid.Ah-Zrwm-retinoic acid and 9-cA-retinoic acid are ligands for retinoic acid receptors (RARs) and retinoid X receptors (RXRs), respectively. The RXRs can form heterodimers with RARs and with the thyroid hormone receptors (TRs), the vitamin D receptor (VDR), and the peroxisome proliferator-activated receptors (PPARs) and a number of other hormone- and nutrient-responsive transcription factors to moderate gene transcription. Because of the ability of RXR to form heterodimers with other nuclear receptors, vitamin A has abroad effect on many hormonally and nutrient-responsive genes.

Retinoids (e.g. retinoic acid) are involved in development and in metabolic regulation (e.g. through induction of expression of PEPCK, the rate limiting enzyme in gluconeogenesis). Retinoic acid derives from retinol, which in turn derives from ingestion of plant a-, 3- and "/-carotenes and other carotenes. Retinoic acid acts via retinoic acid receptors and retinoid X receptors note that these receptors can heterodimerize in the nucleus with other related hormone receptors such as PPA-Rs. The developmental importance of retinoic acid is underscored by the teratogenicity of retinoic acid and other vitamin A related compounds, notably some compounds developed for anti-acne properties. 

Glass CK (1996) Some newtwists in the regulation ofgene expressionby thyroid hormone and retinoic acid receptors. Journal of Endocrinology 150,349-57. 

Retinoic acid receptors bind retinoic acid-, (vitamin A acid), derivatives and regulate gene expression. 

Another forefront technique to improve the function of the stratum corneum and enhance barrier repair in dry skin is the use of epidermal differentiation. A number of hormone receptors for epidermal differentiation have been identified. This family of receptors includes retinoic acid receptors, the steroid receptors, the thyroid receptors, the Vitamin D receptors, the peroxisome proliferator-activated receptors, the farnesol-activated receptors, and the liver-activated receptors. It is reported that these transcription factors bind their respective ligands and regulate many of the aspects of cellular proliferation and differentiation. Examples of ligands for the last three transcription factors are fatty acids for the peroxisome proliferator-activated receptor, famesol for the farnesol-activated receptor, and hydroxylated cholesterol derivatives for the liver-activated receptor. The stimulation of epidermal differentiation stimulated the synthesis of involucrin, filaggrin, and the enzymes of the ceramide synthesis pathway (74). 

Glass, C. K. (1996). Some new twists in the regulation of gene expression by thyroid hormone and retinoic acid receptors, /. EjwfoctiJtoi- ISO, 349-357. 

Retinoic acid receptor DNA binding and genetic regulation... 

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