STAT3 Acts as a Co-activator of Glucocorticoid Receptor Signaling

• DOI: 10.1074/jbc.272.49.30607
• Publication Date: 2002-07-26T14:48:08Z
• Authors: Zhixin Zhang; Simon Jones; James S. Hagood; Nelson L. Fuentes; Gerald M. Fuller
• Keywords: STAT3 Transcription Factor; 0301 basic medicine; Interleukin-6; Drug Synergism; Ligands; Transfection; Rats; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; Liver Neoplasms, Experimental; Receptors, Glucocorticoid; COS Cells; Trans-Activators; Tumor Cells, Cultured; Animals; Glucocorticoids; Signal Transduction

Interleukin-6 (IL-6) and glucocorticoids are important mediators of inflammatory and immunological responses. Glucocorticoids are known to synergistically enhance IL-6-mediated cellular responses. We now show that IL-6 also has a synergistic effect upon glucocorticoid signaling. In particular, IL-6-activated STAT3 associates with ligand-bound glucocorticoid receptor to form a transactivating/signaling complex, which can function through either an IL-6-responsive element or a glucocorticoid-responsive element. These findings reveal a new level of interaction between these two crucial signaling cascades and indicate that activated STAT3 can also act as a transcriptional co-activator without direct association with its DNA binding motif.