We use actual cells to evaluate the functions of nuclear receptor-targeting medicines and food materials from various perspectives.

What is a nuclear receptor?

Steroids, thyroid hormones, vitamin D, retinoic acid, etc. are strongly involved not only in regulation of functions such as cellular proliferation and differentiation, but also in diseases, such as cancer and metabolic syndrome. These low-molecular compounds function by binding to intracellular proteins called nuclear receptors. So far 48 kinds of nuclear receptors have been identified in humans. Different receptors exist in various organs and tissues. These receptors bind to specific substances (ligands) to exert various physiological effects and play roles in various kinds of biological regulation. Because of these effects, receptors have also been attracting attention lately as drug targets.

Nuclear receptors exert their effects by activating expression of specific genes.
Nuclear receptors have a structure consisting of six domains, as shown in the figure below. A/B is a ligand-independent transcriptional activation site. C is a DNA-binding domain (DBD) with two Zn-finger structures. The DBD (DNA-binding domain) recognizes and binds to a specific DNA sequence upstream of the target gene.
Ligand-binding domain (LBD) E has a pocket structure to which a ligand substance binds.

Nuclear receptors that have bound to ligands undergo structural changes that allow them to interact with coactivators. These coactivators presumably act on histone structures and unwind double-stranded DNA to activate transcription via general transcription factors and RNA polymerase. In other words, nuclear receptors, activated by binding to specific ligands, bind to specific DNA sequences to activate transcription of downstream genes. Because of these effects, nuclear receptors are also called "ligand-dependent transcription factors".