Nuclear receptor: Structure and function

Abstract

Ligand-dependent transcription factors are nuclear receptors (NRs) that regulate various critical cellular processes such as reproduction, metabolism, development, etc. NRs are classified into (subgroup 0 to subgroup 6) seven superfamilies based on ligand-binding characteristics. All NRs share a general domain structure (A/B, C, D, and E) with distinct essential functions. NRs as monomers, homodimers, or heterodimers bind to consensus DNA sequences known as Hormone Response Elements (HREs). Furthermore, nuclear receptor-binding efficiency depends on minor differences in the sequences of HREs, spacing between the two half-sites, and the flanking sequence of the response elements. NRs can trans-activate and repress their target genes. In positively regulated genes, ligand-bound NRs recruit coactivators to activate the target gene expression, and unliganded NRs cause transcriptional repression. On the other hand, NRs repress gene expression by different mechanisms: (i) ligand-dependent transcriptional repression, (ii) ligand-independent transcriptional repression. This chapter will briefly explain NR superfamilies, their structures, molecular mechanism of action and their role in pathophysiological conditions, etc. That could enable the discovery of new receptors and their ligands and may elucidate their roles in various physiological processes. In addition, therapeutic agonists and antagonists would be developed to control the dysregulation of nuclear receptor signaling.

Keywords: Hormone response element; Ligand; Nuclear receptor; Trans repression; Transactivation.