PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activityby sequestration into nuclear bodies

The Wnt-responsive transcription factor LEF1 can activate transcription in association with beta -catenin and repress transcription in association wit h Groucho. In search of additional regulatory mechanisms of LEF1 function, we identified the protein inhibitor of activated STAT, PIASy, as a novel in teraction partner of LEF1. Coexpression of PIASy with LEF1 results in poten t repression of LEF1 activity and in covalent modification of LEF1 with SUM O. PIASy markedly stimulates the sumoylation of LEF1 and multiple other pro teins in vivo, and functions as a SUMO E3 ligase for LEF1 in a reconstitute d system in vitro. Moreover, PIASy binds to nuclear matrix-associated DNA s equences and targets LEF1 to nuclear bodies, suggesting that PIASy-mediated subnuclear sequestration accounts for the repression of LEF1 activity.