title: A reduction state potentiates the glucocorticoid response through receptor protein stabilization.
abstract: The intracellular redox state regulates all biological processes including gene expression. The glucocorticoid receptor (GR), a hormone-dependent transcription factor, is affected by the redox state. GR translocation from the cytoplasm to the nucleus is regulated by oxidative stress. The molecular mechanism of how the redox state affects GR transcriptional regulation, however, has not been clarified. We identified a deoxidizing agent, cobalt chloride (CoCl(2)), that potentiates the GR transcriptional effects by stabilizing endogenously expressed GR protein as well as exogenously over-expressed one without affecting GR mRNA level. Consequent GR protein stabilization enhanced co-factor recruitments on the target gene promoters. These results support the existence of a novel redox-dependent mechanism of GR transcriptional regulation mediated by receptor protein stabilization.
authors.affiliation: The Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yamaoka
authors.forename: Chihiro
authors.initials: C
authors.lastname: Akimoto
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kase
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mezaki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010084:Oxidation-Reduction; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003035:Cobalt; D006861:Hydrogen Peroxide; C018021:cobaltous chloride