A transcriptional corepressor of Stat1 with an essential LXXLL signature motif

Interferon (IFN) treatment induces tyrosine phosphorylation and nuclear tra nslocation of Stat1 (signal transducer and activator of transcription) to a ctivate or repress transcription. We report here that a member of the prote in inhibitor of activated STAT family, PIASy, is a transcriptional corepres sor of Stat1. IFN treatment triggers the in viva interaction of Stat1 with PIASy, which represses Stat1-mediated gene activation without blocking the DNA binding activity of Stat1. An LXXLL coregulator signature motif located near the NH2 terminus of PIASy, although not involved in the PIASy-Stat1 i nteraction, is required for the transrepression activity of PIASy. Our stud ies identify PIASy as a transcriptional I corepressor of Stat1 and suggest that different PIAS proteins may repress STAT-mediated gene activation thro ugh distinct mechanisms.