Nuclear Receptors (NRs) are involved in a multitude of biological pathways and numerous disorders and diseases; it would be difficult to find another family of proteins in the human genome that has such a broad and critical role in both healthy and diseased contexts. Further, they constitute the archetypal proteins for studying some of the most fundamental processes of gene regulation and genomic organization. The first NR was cloned in the 1980s, and we now know that this family is comprised of 48 distinct proteins that share common structural properties. They play essential roles in the development of organs, as evidenced by phenotypic consequences following gene deletion. They are also frequently co-opted or altered in disease states, including cancer and metabolic disorders. One of the special features of the NR superfam-ily is the fact that they constitute the only class of readily druggable transcription factors. This makes them critical downstream effectors of numerous biological and cellular processes and also the targets of many treatments and therapies. Their vital role in both healthy and pathological contexts likely results from a relatively unique feature of this class of transcription factors: their ligand activated switchable states.
Jason S. Carroll
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Cancer Research UK Cambridge Research Institute, Cambridge, UK
NSTL
