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.
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Cover Image
Cover Image
Long Terminal Repeat (LTR) retrotransposons replicate through “copy and paste” mechanisms mediated by reverse transcription in virus-like particles (VLPs) and integration in the nucleus (see article from Lee and Martienssen, pp. 2241–2251). VLP DNA-sequencing reveals complementary DNA (cDNA) replication intermediates from active retrotransposons. Instead of functional linear intermediates that integrate in the nucleus, the Arabidopsis retroelement SISYPHUS lacks features important for nuclear import, and instead accumulates circular cDNA from futile autointegration within the VLP. In Greek mythology, Sisyphus was condemned to the futile task of rolling a huge boulder uphill eternally. Image created and provided Seung Cho Lee, Evan Ernst, and Robert A. Martienssen.
Structural insights into glucocorticoid receptor function
Filipp Frank, Eric A. Ortlund, Xu Liu; Structural insights into glucocorticoid receptor function. Biochem Soc Trans 1 November 2021; 49 (5): 2333–2343. doi: https://doi.org/10.1042/BST20210419
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