title: Global analysis of phosphorylation and ubiquitylation cross-talk in protein degradation.
abstract: Cross-talk between different types of post-translational modifications on the same protein molecule adds specificity and combinatorial logic to signal processing, but it has not been characterized on a large-scale basis. We developed two methods to identify protein isoforms that are both phosphorylated and ubiquitylated in the yeast Saccharomyces cerevisiae, identifying 466 proteins with 2,100 phosphorylation sites co-occurring with 2,189 ubiquitylation sites. We applied these methods quantitatively to identify phosphorylation sites that regulate protein degradation via the ubiquitin-proteasome system. Our results demonstrate that distinct phosphorylation sites are often used in conjunction with ubiquitylation and that these sites are more highly conserved than the entire set of phosphorylation sites. Finally, we investigated how the phosphorylation machinery can be regulated by ubiquitylation. We found evidence for novel regulatory mechanisms of kinases and 14-3-3 scaffold proteins via proteasome-independent ubiquitylation.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Swaney
authors.forename: Pedro
authors.initials: P
authors.lastname: Beltrao
authors.forename: Lea
authors.initials: L
authors.lastname: Starita
authors.forename: Ailan
authors.initials: A
authors.lastname: Guo
authors.forename: John
authors.initials: J
authors.lastname: Rush
authors.forename: Stanley
authors.initials: S
authors.lastname: Fields
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.forename: Judit
authors.initials: J
authors.lastname: Villén
mesh_terms: D001665:Binding Sites; D005656:Fungal Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D057149:Ubiquitinated Proteins