title: Osmotic regulation of STAT3 stability in H4IIE rat hepatoma cells.
abstract: Little is known about the regulation of signal transducer and activator of transcription (STAT) stability. Here the osmolarity-dependence of STAT3 stability, ubiquitination, Tyr(705) phosphorylation, STAT3 transactivation and gamma-fibrinogen (gamma-FBG) expression was studied in hepatoma cells. Hyper-osmolarity accelerated STAT3 degradation which was prevented by proteasome inhibitors. Hypo-osmolarity stabilized STAT3, most likely due to a decrease in STAT3 ubiquitination. Accordingly, STAT3 Tyr(705) phosphorylation, alpha(2)-macroglobulin promoter activity and gamma-FBG expression were osmosensitive. Modulation of STAT3 stability may contribute to a hydration dependence of acute phase protein expression.
authors.affiliation: Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum der Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Lornejad-Schäfer
authors.forename: Ute
authors.initials: U
authors.lastname: Albrecht
authors.forename: Diana
authors.initials: D
authors.lastname: Poppek
authors.forename: Thor
authors.initials: T
authors.lastname: Gehrmann
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Bode
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Freimut
authors.initials: F
authors.lastname: Schliess
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D005340:Fibrinogen / Q000235:genetics; D005786:Gene Expression Regulation; D008113:Liver Neoplasms; D009995:Osmosis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D014452:Ubiquitins / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000235:genetics
chemical_list: D061988:Proteasome Inhibitors; D050796:STAT3 Transcription Factor; D014452:Ubiquitins; D000511:alpha-Macroglobulins; D005340:Fibrinogen; D046988:Proteasome Endopeptidase Complex