Dual role for SUMO E2 conjugase Ubc9 in modulating the transforming and growth-promoting properties of the HMGA1b architectural transcription factor

Abstract

Members of the HMGA1 (high mobility group A1) family of architectural transcription factors, HMGA1a and HMGA1b, play important roles in many normal cellular processes and in tumorigenesis. We performed a yeast two-hybrid screen for HMGA1-interacting proteins and identified the SUMO E2 conjugase Ubc9 as one such partner. The Ubc9-interacting domain of HMGA1 is bipartite, consisting of a proline-rich region near the N terminus and an acidic domain at the extreme C terminus, whereas the HMGA1-interacting domain of Ubc9 comprises a single region previously shown to associate with and SUMOylate other transcription factors. Consistent with these findings, endogenous HMGA1 proteins and Ubc9 could be co-immunoprecipitated from several human cell lines. Studies with HMGA1b proteins containing mutations of either or both Ubc9-interacting domains and with Ubc9-depleted cell lines indicated that the proline-rich domain of HMGA1b positively influences transformation and growth, whereas the acidic domain negatively influences these properties. None of the changes in HMGA1 protein functions mediated by Ubc9 appears to require SUMOylation. These findings are consistent with the idea that Ubc9 can act as both a positive and negative regulator of proliferation and transformation via its non-SUMO-dependent interaction with HMGA1 proteins.