Nuclear receptor superfamily (NR superfamily) (NR)

The nuclear receptor superfamily is a diverse group of ligand-gated transcription factors that play pivotal roles in regulating gene expression in response to various physiological signals, including steroid hormones, thyroid hormones, and lipid-soluble vitamins (Mangelsdorf et al., 1995, Cell; IUPHAR/BPS Guide to Pharmacology). These receptors share a modular structure typically consisting of a highly conserved DNA-binding domain and a C-terminal ligand-binding domain (Sever & Glass, 2013, Cold Spring Harbor Perspectives in Biology). Upon ligand binding, these receptors undergo conformational changes that facilitate their translocation to the nucleus, binding to specific hormone response elements in the genome, and the recruitment of co-regulatory complexes to modulate transcription (NCBI Gene). Members of this family, such as the estrogen receptors and peroxisome proliferator-activated receptors, are critical therapeutic targets in oncology, endocrinology, and metabolic diseases (Burris et al., 2013, Pharmacological Reviews). Drugs targeting these receptors include selective receptor modulators, agonists, and antagonists, which are used to treat conditions ranging from breast cancer to type 2 diabetes (PubChem). However, the high structural homology between different nuclear receptors often presents challenges in achieving high selectivity, potentially leading to off-target effects and endocrine-related safety concerns (StatPearls).

Other names

Nuclear hormone receptorsLigand-activated transcription factorsSteroid receptorsEstrogen receptors and related nuclear receptorsNR superfamily

Ligand-dependent modulation of gene transcription through DNA binding and recruitment of co-activators or co-repressors (IUPHAR/BPS Guide to Pharmacology).