Retinoic Acid and Retinoid X Receptors Antibody Sampler Kit

Background

Nuclear retinoic acid (RA) receptors (RARs) consist of three subtypes encoded by separate genes: α (NR1B1), β (NR1B2), and γ (NR1B3). For each subtype, there are at least two isoforms, which are generated by differential promoter usage and alternative splicing and differ only in their N-terminal regions. Retinoids, which are metabolites of vitamin A, serve as ligands for RARs (1). RARs function as ligand-dependent transcriptional regulators and are found to be heterodimerized with retinoid X receptors (RXRs). These transcriptionally active dimers regulate the expression of genes involved in cellular differentiation, proliferation, and apoptosis (2,3). Consequently, RARs play critical roles in a variety of biological processes, including development, reproduction, immunity, and organogenesis (4-6). RAR mutations, fusion proteins, altered expression levels, or aberrant post-translational modifications result in multiple diseases due to altered RAR function and disruption of homeostasis.

In contrast to the ubiquitously expressed RARα subtype, RARγ displays a complex tissue-specific expression pattern (7). The hematopoietic system expresses significant levels of RARγ, and a recent study identified a role for RARγ in hematopoietic stem cell maintenance (8). RARγ is the predominant subtype in human and mouse epidermis, representing 90% of the RARs in this tissue (9-11). Given the high level of RARγ expression in the skin, it has been suggested that this nuclear receptor participates in a transcriptional program that governs maintenance and differentiation of normal epidermis and skin appendages. The transcriptional activity of RARγ is under stringent control, in part, through retinoic acid-induced phosphorylation and proteasomal degradation (12).

The human retinoid X receptors (RXRs) are encoded by three distinct genes (RXRα, RXRβ, and RXRγ) and bind selectively and with high affinity to the vitamin A derivative, 9-cis-retinoic acid. RXRs are type-II nuclear hormone receptors that are largely localized to the nuclear compartment independent of ligand binding. Nuclear RXRs form heterodimers with nuclear hormone receptor subfamily 1 proteins, including thyroid hormone receptor, retinoic acid receptors, vitamin D receptor, peroxisome proliferator-activated receptors, liver X receptors, and farnesoid X receptor (13). Since RXRs heterodimerize with multiple nuclear hormone receptors, they play a central role in transcriptional control of numerous hormonal signaling pathways by binding to cis-acting response elements in the promoter/enhancer region of target genes (14).