Modulation of Glucocorticoid Receptor Induction Properties by Cofactors in Peripheral Blood Mononuclear Cells
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Glucocorticoids are widely used for their anti-inflammatory and immunosuppressive properties. Changing concentrations of transcriptional cofactors or chemicals in transiently transfected tissue culture cells modify several properties of glucocorticoid receptor-regulated gene expression including total activity (A(max)), agonist steroid potency (EC(50)), and the percentage of full agonist activity for antisteroids (percent partial agonist activity). However, no reports exist for endogenous genes in primary human cells. Here we document that reduced concentrations of TIF2, a p160 coactivator, in peripheral blood mononuclear cells modulate these parameters for endogenous genes in a gene-selective manner, thus establishing the physiological relevance of this behavior.
An Approach to Greater Specificity for Glucocorticoids.
Chow C, Simons Jr S Front Endocrinol (Lausanne). 2018; 9:76.
PMID: 29593646 PMC: 5859375. DOI: 10.3389/fendo.2018.00076.
Pradhan M, Blackford Jr J, Devaiah B, Thompson P, Chow C, Singer D J Biol Chem. 2015; 291(1):342-54.
PMID: 26504077 PMC: 4697169. DOI: 10.1074/jbc.M115.683722.
Theory of partial agonist activity of steroid hormones.
Chow C, Ong K, Kagan B, Simons Jr S AIMS Mol Sci. 2015; 2(2):101-123.
PMID: 25984562 PMC: 4430866. DOI: 10.3934/molsci.2015.2.101#sthash.jxRCteJz.dpuf.
Blackford Jr J, Brimacombe K, Dougherty E, Pradhan M, Shen M, Li Z Mol Endocrinol. 2014; 28(7):1194-206.
PMID: 24850414 PMC: 4075162. DOI: 10.1210/me.2014-1069.
Minireview: dynamic structures of nuclear hormone receptors: new promises and challenges.
Simons Jr S, Edwards D, Kumar R Mol Endocrinol. 2013; 28(2):173-82.
PMID: 24284822 PMC: 3896641. DOI: 10.1210/me.2013-1334.