Article
- The EMBO Journal (2006) 25, 5083 - 5093
- doi:10.1038/sj.emboj.7601383
Published online: 12 October 2006
Subject Categories:
An extended consensus motif enhances the specificity of substrate modification by SUMO
Shen-Hsi Yang, Alex Galanisab, James Wittya and Andrew D Sharrocks
- Faculty of Life Sciences, University of Manchester, Manchester, UK
Correspondence to:
Andrew D Sharrocks, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. Tel.: +44 161 275 5979; Fax: +44 161 275 5082; E-mail: a.d.sharrocks@manchester.ac.uk
aThese authors contributed equally to this work
bPresent address: Laboratory of Gene Expression, Molecular Diagnostics and Modern Therapeutics, Department of Molecular Biology and Genetics, Democritus University of Thrace, Dimitras 19, Alexandroupolis 68100, Greece
Received 21 April 2006; Accepted 18 September 2006
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 
KxE. 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.
Keywords:
- Elk-1,
- SUMO,
- transcription repression,
- Ubc9
