title: An extended consensus motif enhances the specificity of substrate modification by SUMO.
abstract: Protein modification by SUMO conjugation is an important regulatory event. Sumoylation usually takes place on a lysine residue embedded in the core consensus motif psiKxE. However, this motif confers limited specificity on the sumoylation process. Here, we have probed the roles of clusters of acidic residues located downstream from the core SUMO modification sites in proteins such as the transcription factor Elk-1. We demonstrate that these are functionally important in SUMO-dependent transcriptional repression of Elk-1 transcriptional activity. Mechanistically, the acidic residues are important in enhancing the efficiency of Elk-1 sumoylation by Ubc9. Similar mechanisms operate in other transcription factors and phosphorylation sites can functionally substitute for acidic residues. Thus, an extended sumoylation motif, termed the NDSM (negatively charged amino acid-dependent sumoylation motif), helps define functional SUMO targets. We demonstrate that this extended motif can be used to correctly predict novel targets for SUMO modification.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Shen-Hsi
authors.initials: SH
authors.lastname: Yang
authors.forename: Alex
authors.initials: A
authors.lastname: Galanis
authors.forename: James
authors.initials: J
authors.lastname: Witty
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Sharrocks
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000235:genetics; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: C494112:ELK1 protein, human; D025842:SUMO-1 Protein; D050807:ets-Domain Protein Elk-1; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9