SPECIFIC-INHIBITION OF STAT3 SIGNAL-TRANSDUCTION BY PIAS3

The signal transducer and activator of transcription-3 (Stat3) protein is activated by the interleukin 6 (IL-6) family of cytokines, epiderm al growth factor, and leptin. A protein named PIAS3 (protein inhibitor of activated STAT) that binds to Stat3 was isolated and characterized . The association of PIAS3 with Stat3 in vivo was only observed in cel ls stimulated with ligands that cause the activation of Stat3. PIAS3 b locked the DNA-binding activity of Stat3 and inhibited Stat3-mediated gene activation. Although Stat1 is also phosphorylated in response to IL-6, PIAS3 did not interact with Stat1 or affect its DNA-binding or t ranscriptional activity. The results indicate that PIAS3 is a specific inhibitor of Stat3.