Retinoid Inhibits Nrf2 Signaling Pathway through Retinoic Acid Receptor Alpha
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Retinoids, natural and synthetic signaling molecules that are structurally related to vitamin A. Compounds such as retinol, retinal, retinoic acid, retinyl esters and other derivatives are considered under the group of retinoids. Retinoids are significantly considered to be the most prominent regulators of several essential biological functions. For instance, active derivative of retinol (metabolite of Vitamin A) such as retinoic acid (RA) plays a major role in vision, cell differentiation, tissue homeostasis, apoptosis, organogenesis, regulation of immune system and embryonic pattern formation(1). In addition RA is also considered to be a potent chemopreventive and tumor suppressive agent because of its apoptotic and anti-oxidant…show more content… These isoforms are formed because of differential usage of promoters and alternative splicing (8). As most, nuclear receptors including retinoid receptors possess similarities in their structural organization. Based on homology with other nuclear receptors, RAR and RXR receptors consists six conserved regions known as A–F. The N terminal region contains two domains (A/B) are designated as AF1 and they are the least conserved domains and highly variable in length which exhibit a ligand-independent transactivation activity. So far, there is no three dimensional structure has been predicted for A/B domain. (9).
Central region-C possess DNA-binding domain (DBD) which is said to be the most conserved region and possess similarity in their structure. DBD contains an important short motif known as P-box which is responsible for direct DNA interaction and detection of specificity for DNA-binding. DBD also possess additional sequences that are required for the homo or heterodimerization of nuclear receptors. A pair of zinc fingers present in domain C is critically responsible for DNA specific contacts and interaction. Domain D is the less conserved domain among nuclear receptors which acts as a flexible hinge in between two domains such as C (DBD) and E (LBD) domains. In addition, domain D possesses the nuclear localization signal (NLS) that regulates the sub cellular distribution of nuclear receptors. The E region contains ligand-binding domain (LBD) is