Mechanism of action of the glucocorticoid receptor. Essential role of TPR-domain immnunophilins

GALIGNIANA MD

Glucocorticoid Receptor and its Role in Health and Disease

Nova Publishers

Año: 2022; p. 40 - 79

Glucocorticoid steroids play essential roles during the life span of an individual modulating carbohydrate metabolism, immune response, inflammation, stress adaptation and cell fate, among other several pleitropic actions. These hormones exert their biological actions through the glucocorticoid receptor (GR), a bona fide ligand-activated transcription factor belonging to the nuclear receptor superfamily. GR is expressed in virtually all cells of the human body. Nonetheless, several biological actions of the glucocorticoid hormones can be specific and sometimes antagonistic to certain tissues and cell types, which implies the existence of regulatory mechanisms that handle the GR-mediated biologic response. The recent discovery that the chaperone complex based on the 90-kDa heat-shock protein (Hsp90) and a TPR-domain immunophilin play an essential role in the GR transport to the nucleus and the nuclear retention half-life opened new trends in our understanding of the tissue-specific mechanism of action of the GR, thus offering new therapeutic opportunities to manage patients? disease In this chapter, we dissect the novel aspects of the GR mechanism of action covering the latest findings that reveal the roles of Hsp90-binding immunophilins managing the glucocorticoid action and how these proteins influence the final biological response.