Comprehensive identification of substrates for F-box proteins by differential proteomics analysis.

Although elucidation of enzyme-substrate relations is fundamental to the advancement of biology, universal approaches to the identification of substrates for a given enzyme have not been established. It is especially difficult to identify substrates for ubiquitin ligases, given that most such substrates are immediately ubiquitylated and degraded as a result ...
of their association with the enzyme. We here describe the development of a new approach, DiPIUS (differential proteomics-based identification of ubiquitylation substrates), to the discovery of substrates for ubiquitin ligases. We applied DiPIUS to Fbxw7α, Skp2, and Fbxl5, three of the most well-characterized F-box proteins, and identified candidate substrates including previously known targets. DiPIUS is thus a powerful tool for unbiased and comprehensive screening for substrates of ubiquitin ligases.
Mesh Terms:
Animals, F-Box Proteins, HEK293 Cells, HeLa Cells, Humans, Immunoprecipitation, Mice, Protein Binding, Protein Interaction Mapping, Proteolysis, Proteomics, SKP Cullin F-Box Protein Ligases, Ubiquitinated Proteins, Ubiquitination
J. Proteome Res.
Date: Jun. 01, 2012
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