title: Uncovering global SUMOylation signaling networks in a site-specific manner.
abstract: SUMOylation is a reversible post-translational modification essential for genome stability. Using high-resolution MS, we have studied global SUMOylation in human cells in a site-specific manner, identifying a total of >4,300 SUMOylation sites in >1,600 proteins. To our knowledge, this is the first time that >1,000 SUMOylation sites have been identified under standard growth conditions. We quantitatively studied SUMOylation dynamics in response to SUMO protease inhibition, proteasome inhibition and heat shock. Many SUMOylated lysines have previously been reported to be ubiquitinated, acetylated or methylated, thus indicating cross-talk between SUMO and other post-translational modifications. We identified 70 phosphorylation and four acetylation events in proximity to SUMOylation sites, and we provide evidence for acetylation-dependent SUMOylation of endogenous histone H3. SUMOylation regulates target proteins involved in all nuclear processes including transcription, DNA repair, chromatin remodeling, precursor-mRNA splicing and ribosome assembly.
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ivo A
authors.initials: IA
authors.lastname: Hendriks
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
authors.forename: Rochelle C J
authors.initials: RC
authors.lastname: D'Souza
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Matty
authors.initials: M
authors.lastname: Verlaan-de Vries
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Alfred C O
authors.initials: AC
authors.lastname: Vertegaal
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D042822:Genomic Instability; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058207:Sumoylation / Q000235:genetics*
chemical_list: D006657:Histones; D061988:Proteasome Inhibitors; D025841:Small Ubiquitin-Related Modifier Proteins; D046988:Proteasome Endopeptidase Complex