Glucocorticoid receptor mutants: man-made tools for functional research

被引:37
作者
Beck, Ilse M. [1 ]
De Bosscher, Karolien [1 ]
Haegeman, Guy [1 ]
机构
[1] Univ Ghent, Dept Physiol, LEGEST, B-9000 Ghent, Belgium
关键词
NF-KAPPA-B; LIGAND-BINDING DOMAIN; STEROID-HORMONE RECEPTORS; GASTRIC-ACID-SECRETION; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; NUCLEAR EXPORT; GENE-EXPRESSION; HSP90; BINDING; HINGE REGION;
D O I
10.1016/j.tem.2011.03.009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that can bind to glucocorticoids (GCs). Upon ligand binding, GR sheds its cytoplasmic chaperoning complex and translocates to the nucleus, where it can act as a ligand-dependent transcription factor, transactivating or transrepressing specific gene promoters. Often, GR interacts with specific cofactors to implement a variety of gene promoter effects. GR activity and function is further modulated by post-translational modifications. To assess the diverse aspects of GR mechanisms of activation and gene regulation, researchers continue to use a range of artificial GR mutants. In this review we analyze the characteristics of GR mutants with the aim of assisting the design and interpretation of GR mutant-based experiments.
引用
收藏
页码:295 / 310
页数:16
相关论文
共 106 条
[1]   Homodimerization of the glucocorticoid receptor is not essential for response element binding:: Activation of the phenylethanolamine N-methyltransferase gene by dimerization-defective mutants [J].
Adams, M ;
Meijer, OC ;
Wang, JA ;
Bhargava, A ;
Pearce, D .
MOLECULAR ENDOCRINOLOGY, 2003, 17 (12) :2583-2592
[2]   DNA-BINDING ANALYSIS OF GLUCOCORTICOID RECEPTOR SPECIFICITY MUTANTS [J].
ALROY, I ;
FREEDMAN, LP .
NUCLEIC ACIDS RESEARCH, 1992, 20 (05) :1045-1052
[3]   Subcellular localization and mechanisms of nucleocytoplasmic trafficking of steroid receptor coactivator-1 [J].
Amazit, L ;
Alj, Y ;
Tyagi, RK ;
Chauchereau, A ;
Loosfelt, H ;
Pichon, C ;
Pantel, J ;
Guinchard, EF ;
Leclerc, P ;
Milgrom, E ;
Guiochon-Mantel, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (34) :32195-32203
[4]   Phosphatidylinositol 3-kinase interacts with the glucocorticoid receptor upon TLR2 activation [J].
Arancibia, Sergio ;
Benitez, Dixan ;
Nunez, Lucia E. ;
Jewell, Christine M. ;
Langjahr, Patricia ;
Candia, Enzo ;
Zapata-Torres, Gerald ;
Cidlowski, John A. ;
Gonzalez, Maria-Julieta ;
Hermoso, Marcela A. .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2011, 15 (02) :339-349
[5]   Role of ligand-dependent GR phosphorylation and half-life in determination of ligand-specific transcriptional activity [J].
Avenant, Chanel ;
Ronacher, Katharina ;
Stubsrud, Elisabeth ;
Louw, Ann ;
Hapgood, Janet P. .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2010, 327 (1-2) :72-88
[6]   Glucocorticoid Receptor Phosphorylation Modulates Transcription Efficacy through GRIP-1 Recruitment [J].
Avenant, Chanel ;
Kotitschke, Andrea ;
Hapgood, Janet P. .
BIOCHEMISTRY, 2010, 49 (05) :972-985
[7]   Glucocorticoid receptor is required for skin barrier competence [J].
Bayo, Pilar ;
Sanchis, Ana ;
Bravo, Ana ;
Cascallana, Jose Luis ;
Buder, Katrin ;
Tuckermann, Jan ;
Schuetz, Guenther ;
Perez, Paloma .
ENDOCRINOLOGY, 2008, 149 (03) :1377-1388
[8]   Crosstalk in Inflammation: The Interplay of Glucocorticoid Receptor-Based Mechanisms and Kinases and Phosphatases [J].
Beck, Ilse M. E. ;
Vanden Berghe, Wim ;
Vermeulen, Linda ;
Yamamoto, Keith R. ;
Haegeman, Guy ;
De Bosscher, Karolien .
ENDOCRINE REVIEWS, 2009, 30 (07) :830-882
[9]   Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-κB inhibition [J].
Beck, Ilse Me ;
Vanden Berghe, Wim ;
Vermeulen, Linda ;
Bougarne, Nadia ;
Cruyssen, Bert Vander ;
Haegeman, Guy ;
De Bosscher, Karolien .
EMBO JOURNAL, 2008, 27 (12) :1682-1693
[10]   Identification of endogenous glucocorticoid repressed genes differentially regulated by a glucocorticoid receptor mutant able to separate between nuclear factor-κB and activator protein-1 repression [J].
Bladh, LG ;
Lidén, J ;
Dahlman-Wright, K ;
Reimers, M ;
Nilsson, S ;
Okret, S .
MOLECULAR PHARMACOLOGY, 2005, 67 (03) :815-826