Response element, retinoid vitamin

Retinoic acid (RA) describes a group of vitamin A acid (synonym Vitamin A1 acid) derivatives such as all-irans-retinoic acid (tretinoin), 9-cis-retinoic acid and 13-cis retinoic acid (isotretinoin). Retinoic acids act through binding to retinoic acid and retinoid X response elements. 

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. 

The form of vitamin A that is needed for regulating vitamin A-dependent gene expression is retinoic acid.All-fraws-retinoic acid can interact with each of the three RARs (RARa, RAR(3, and RARy) and each of the three RXRs (RXRa, RXR(3, and RXRy). 9-cX-Retinoic acid binds and effectively transactivates only the RXRs. The RARs and the RXRs recognize well-defined exacting response elements, termed retinoic acid response elements (RAREs) and retinoid X response elements (RXREs) that are present in the promoter regions of responsive genes. The RARs and RXRs bind to RAREs and/or RXREs as dimers, either homodimers or heterodimers. 

The vitamin D receptor acts mainly as a heterodimer with the retinoid X receptor (RXR Section 2.3.2.1). Binding of calcitriol induces a conformational change in the receptor protein, permitting dimerization with occupied or unoccupied RXR, followed by phosphorylation to activate binding to the vitamin D response element on DNA (DeLuca and Zierold, 1998). Abnormally high concentrations of 9-cis-retinoic acid result in sequestration of RXR as the homodimers, meaning that it is unavailable to form heterodimers with the vitamin D receptor (or other receptors) excessive vitamin A can therefore antagonize the nuclear actions of vitamin D (Haussler et al., 1995 Rohde et al., 1999). 

Mackey, S. L-, Heymont,). L-, Kionenberg, H. M., and Dcmay, M. B. (1996), Vitamin D receptor binding to the negative human parathyroid hormone vitamin D response element does not require the retinoid X receptor, Mof. Endocrine . ID, 298-305. 

Zou, A., Elgort, M, G and Allegnelto, E. A. (1997). Retinoid X receptor (RXR) ligands activate the human 25-hydroJtyvitarnift D 24 hydroxylase promoter via RXR heterodimer binding to two vitamin L -reSponsive elements and elicit additive effects with 1,25-dihydroxy vitamin D i. J. Biol. Climi. 272, 19027-19054. 

Heterodlmeric nuclear receptors (e.g., those for retinoids, vitamin D, and thyroid hormone) are found only in the nucleus. In the absence of hormone, they repress transcription of target genes with the corresponding response element. When bound to their ligands, they activate transcription. 

The active form of vitamin D, 1,25 dihydroxy-vitamin D (l,25(OH)2D), binds to the vitamin D receptor (VDR), which is expressed in most cells. l,25(OH)2D functions as a steroid hormone, usually by heterodimerization with the retinoid X receptor, binding to vitamin-D response elements (VDRE) located in promoter regions. It induces the expression of target genes involved in many cellular responses, including the immune responses. 

Umesono K, Murakami KK, Thompson CC, Evans RM (1991) Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 65 1255-1266 Carlberg C (1995) Mechanisms of nuclear signalling by vitamin D3 interplay with retinoid and thyroid hormone signalling. EurJ Biochem 231 517-527... 

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