Weikum Emily R, Knuesel Matthew T, Ortlund Eric A, Yamamoto Keith R
Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
Department of Cellular and Molecular Pharmacology, University of California San Francisco School of Medicine, 600 16th Street, San Francisco, California 94143, USA.
Nat Rev Mol Cell Biol. 2017 Mar;18(3):159-174. doi: 10.1038/nrm.2016.152. Epub 2017 Jan 5.
The glucocorticoid receptor (GR) is a constitutively expressed transcriptional regulatory factor (TRF) that controls many distinct gene networks, each uniquely determined by particular cellular and physiological contexts. The precision of GR-mediated responses seems to depend on combinatorial, context-specific assembly of GR-nucleated transcription regulatory complexes at genomic response elements. In turn, evidence suggests that context-driven plasticity is conferred by the integration of multiple signals, each serving as an allosteric effector of GR conformation, a key determinant of regulatory complex composition and activity. This structural and mechanistic perspective on GR regulatory specificity is likely to extend to other eukaryotic TRFs.
糖皮质激素受体(GR)是一种组成性表达的转录调节因子(TRF),它控制着许多不同的基因网络,每个基因网络都由特定的细胞和生理环境独特地决定。GR介导的反应的精确性似乎取决于基因组反应元件处GR核化转录调节复合物的组合性、上下文特异性组装。反过来,有证据表明,上下文驱动的可塑性是由多种信号的整合赋予的,每种信号都作为GR构象的变构效应器,而GR构象是调节复合物组成和活性的关键决定因素。这种关于GR调节特异性的结构和机制观点可能会扩展到其他真核生物的TRF。