Potentiation of Tbx5-mediated transactivation by SUMO conjugation and protein inhibitor of activated STAT 1 (PIAS1)

The role of the T-box transcription factor Tbx5 in heart and limb development has been well documented; however, how posttranslational modification is involved in mediating its activity is unknown. Here we report that Tbx5 is a novel target by SUMO conjugation, a posttranslational modification that is involved in a variety of cellular events. Sumoylation potentiated the transcriptional activity of Tbx5, and PIAS family members, a group of SUMO E3 ligase, differentially mediated sumoylation and function of Tbx5. PIAS1 potently stimulated SUMO conjugation to Tbx5, and the physical association of Tbx5 with PIAS1 was required for its full sumoylation. PIAS1 also enhanced the functional cooperation between Tbx5 and its interaction partners. Overlapping expression pattern and colocalization of PIAS1 and Tbx5 in the mouse embryonic hearts and on the native target gene promoter were observed, pointing to a potential functional interaction of these two factors in vivo. These findings provide novel insights into how the transcriptional activity of a cardiac-specific factor, Tbx5, is regulated both directly and indirectly via posttranslational modification by a non-tissue-specific factor, PIAS1. (C) 2014 Elsevier Ltd. All rights reserved.