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, Tyr⁷⁰⁵ phosphorylation, STAT3 transactivation and γ-fibrinogen (γ-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 Tyr⁷⁰⁵ phosphorylation, α₂-macroglobulin promoter activity and γ-FBG expression were osmosensitive. Modulation of STAT3 stability may contribute to a hydration dependence of acute phase protein expression. [Copyright &y& Elsevier]