Nuclear Receptor Genes (NR Superfamily) encode over 300 ligand-dependent Nuclear Receptor (NRs) transcription factors: steroid, retinoid, vitamin D, TH, and orphan receptors (unknown ligands). Transducing hormone signals into gene transcription, NRs regulate development, pattern formation, cell proliferation, cell differentiation, and homeostasis in target tissues. NRs share a common organization: an (N) modulatory domain, a conserved central Cys-rich region of two C4 zinc fingers that bind to specific upstream ligand-responsive target DNA elements, and a (C) ligand-binding domain. Stabilizing hydrophobic zinc finger interactions contribute to DNA binding specificity, homodimerization, and interaction with other proteins. Ligand-bound NR conformation allows coactivator interaction with the hormone-binding domain that mediates interaction with heat shock proteins, cyclophilins, and hormone. (NCI) [ ]