title: 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.
authors.affiliation: Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom. lynn.powell@ed.ac.uk
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Powell
authors.forename: Angela
authors.initials: A
authors.lastname: Chen
authors.forename: Yan Chang
authors.initials: YC
authors.lastname: Huang
authors.forename: Pin Yao
authors.initials: PY
authors.lastname: Wang
authors.forename: Sadie E
authors.initials: SE
authors.lastname: Kemp
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Jarman
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017344:Genes, Insect; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008959:Models, Neurological; D016297:Mutagenesis, Site-Directed; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012679:Sense Organs / Q000254:growth & development / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D008239:Lysine; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; C413162:sens protein, Drosophila