Glucocorticoid receptor signaling: intricacies and therapeutic opportunities

被引：10

作者：

Clarisse, Dorien ^{[1
,2
,3
]}

Van Moortel, Laura ^{[1
,2
,3
]}

Van Leene, Chloe ^{[1
,2
,3
]}

Gevaert, Kris ^{[1
,2
,3
]}

De Bosscher, Karolien ^{[1
,2
,3
]}

机构：

[1] VIB Ctr Med Biotechnol, Ghent, Belgium

[2] Univ Ghent, Dept Biomol Med, Ghent, Belgium

[3] Canc Res Inst Ghent, Ghent, Belgium

来源：

TRENDS IN BIOCHEMICAL SCIENCES | 2024年 / 49卷 / 05期

关键词：

CHROMATIN ACCESSIBILITY; DNA-BINDING; COACTIVATOR; MECHANISMS; REPRESSION; CROSSTALK; DYNAMICS; TARGET; BREAST; SITE;

D O I：

10.1016/j.tibs.2024.01.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The glucocorticoid receptor (GR) is a major nuclear receptor (NR) drug target for the treatment of inflammatory disorders and several cancers. Despite the effectiveness of GR ligands, their systemic action triggers a plethora of side effects, limiting long-term use. Here, we discuss new concepts of and insights into GR mechanisms of action to assist in the identification of routes toward enhanced therapeutic benefits. We zoom in on the communication between different GR domains and how this is influenced by different ligands. We detail findings on the interaction between GR and chromatin, and highlight how condensate formation and coregulator confinement can perturb GR transcriptional responses. Last, we discuss the potential of novel ligands and the therapeutic exploitation of crosstalk with other NRs.

引用

页码：431 / 444

页数：14

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