RXRA

Retinoid X receptor alpha (RXR-α) is a member of the nuclear receptor superfamily encoded by the RXRA gene in humans. RXR-α functions as a ligand-activated transcription factor that regulates gene expression by forming DNA-binding heterodimers with a broad set of other nuclear receptors. It is widely expressed across tissues and participates in signaling pathways that coordinate development, metabolism, and cell differentiation.

Structure and mechanism: RXR-α contains a DNA-binding domain with zinc finger motifs and a ligand-binding domain. It binds ligands such as 9-cis retinoic acid, though its activity is often determined by the partner receptor in the heterodimer. RXR-α commonly forms heterodimers with peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptor (FXR), vitamin D receptor, and retinoic acid receptor (RAR), among others. In non-permissive heterodimers (for example, RAR-RXR), activation requires the partner receptor; in permissive heterodimers (such as PPAR-RXR or LXR-RXR), RXR ligands can enhance transcription.

Function: Through these partnerships, RXR-α regulates genes involved in lipid and glucose metabolism, adipogenesis, cholesterol homeostasis, and cellular differentiation. It also contributes to embryonic development and organogenesis in tissues such as the eye, nervous system, and adipose tissue.

Clinical significance: Altered RXR signaling has been associated with metabolic disorders and cancer. Pharmacologic agonists targeting RXR, such as bexarotene, are approved for certain cancers (notably cutaneous T-cell lymphoma) and are studied for potential roles in metabolic disease and oncology. Side effects of RXR-targeting therapies can include lipid disturbances and thyroid-related effects.

Genetics and regulation: RXRA expression is regulated by developmental and environmental cues. The receptor interacts with coactivators and corepressors to modulate transcription and can be subject to post-translational modifications that influence its activity. Dysregulation of RXR signaling can impact differentiation, metabolism, and cell proliferation.