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Global analysis of phosphorylation and ubiquitylation cross-talk in protein degradation.

Nat Methods.. 2013-06; 
Swaney DL, Beltrao P, Starita L, Guo A, Rush J, Fields S, Krogan NJ, Villen J. Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
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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 ... More