Open AccessStructural insights into glucocorticoid receptor function
Author(s) -
Filipp Frank,
Eric A. Ortlund,
Xu Liu
Publication year - 2021
Publication title -
biochemical society transactions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.562
H-Index - 144
eISSN - 1470-8752
pISSN - 0300-5127
DOI - 10.1042/bst20210419
Subject(s) - glucocorticoid receptor , glucocorticoid , transcription factor , hormone response element , context (archaeology) , biology , nuclear receptor , steroid hormone , function (biology) , transcription (linguistics) , microbiology and biotechnology , receptor , gene , computational biology , genetics , endocrinology , paleontology , cancer , estrogen receptor , breast cancer , linguistics , philosophy
The glucocorticoid receptor (GR) is a steroid hormone-activated transcription factor that binds to various glucocorticoid response elements to up- or down- regulate the transcription of thousands of genes involved in metabolism, development, stress and inflammatory responses. GR consists of two domains enabling interaction with glucocorticoids, DNA response elements and coregulators, as well as a large intrinsically disordered region that mediates condensate formation. A growing body of structural studies during the past decade have shed new light on GR interactions, providing a new understanding of the mechanisms driving context-specific GR activity. Here, we summarize the established and emerging mechanisms of action of GR, primarily from a structural perspective. This minireview also discusses how the current state of knowledge of GR function may guide future glucocorticoid design with an improved therapeutic index for different inflammatory disorders.