The SUMO Pathway Promotes Basic Helix-Loop-Helix Proneural Factor Activity via a Direct Effect on the Zn Finger Protein Senseless

Abstract

During development, proneural transcription factors of the basic helix-loop-helix (bHLH) family are required to commit cells to a neural fate. In Drosophila neurogenesis, a key mechanism promoting sense organ precursor (SOP) fate is the synergy between proneural factors and their coactivator Senseless in transcriptional activation of target genes. Here we present evidence that posttranslational modification by SUMO enhances this synergy via an effect on Senseless protein. We show that Senseless is a direct target for SUMO modification and that mutagenesis of a predicted SUMOylation motif in Senseless reduces Senseless/proneural synergy both in vivo and in cell culture. We propose that SUMOylation of Senseless via lysine 509 promotes its synergy with proneural proteins during transcriptional activation and hence regulates an important step in neurogenesis leading to the formation and maturation of the SOPs.

ACKNOWLEDGMENTS

We are grateful to Minghua Nie, Matthew Smith, and Albert Courey for fly lines and expression constructs for the S2 cell assays. We thank Johannes Bischof, Terence Murphy, Hamed Jafar-Nejad, and Christos Delidakis for plasmid constructs. We thank Giusy Pennetta, Paul Skehel, Petra zur Lage, and other members of the Jarman lab for their helpful comments on the paper.

This work was supported by grants from the Medical Science and Technology Center, the Aim for the Top University Plan, National Sun Yat-Sen University, Kaohsiung, Taiwan, and Wellcome Trust grant no. 089539.