STAT3 acts as a co-activator of glucocorticoid receptor signaling.
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.
Zhang
Z
Z
Department of Cell Biology, Pulmonary Division, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Jones
S
S
Hagood
J S
JS
Fuentes
N L
NL
Fuller
G M
GM
D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008024:Ligands; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D015850:Interleukin-6; D008024:Ligands; D011965:Receptors, Glucocorticoid; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators