LXR-α Protein, Human

LXR-α Protein, a nuclear receptor, displays ligand-dependent transcriptional activation activity, and its interaction with retinoic acid receptor (RXR) transforms RXR into an active ligand-binding subunit, mediating retinoid responses through target genes defined by LXRES. These LXRES consist of DR4-type response elements characterized by direct repeats of two similar hexanucleotide half-sites spaced by four nucleotides. A pivotal player in cholesterol homeostasis, LXR-α regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR, and LRP8. Functionally interacting with RORA, it contributes to the regulation of genes involved in liver metabolism. Moreover, LXR-α induces LPCAT3-dependent phospholipid remodeling in hepatocyte endoplasmic reticulum membranes, facilitating SREBF1 processing and lipogenesis. Through LPCAT3, it promotes the incorporation of arachidonate into phosphatidylcholines, enhancing membrane dynamics and enabling the transfer of triacylglycerols to nascent very low-density lipoprotein particles. Additionally, LXR-α, via LPCAT3, counteracts lipid-induced ER stress response and inflammation by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators. Forming a heterodimer with NR1H3 and RXR, LXR-α also interacts with CCAR2, SIRT1, and GPS2, further illustrating its intricate regulatory network.