Open AccessProteomic snapshot of the EGF‐induced ubiquitin network
Author(s) -
Argenzio Elisabetta,
Bange Tanja,
Oldrini Barbara,
Bianchi Fabrizio,
Peesari Raghunath,
Mari Sara,
Di Fiore Pier Paolo,
Mann Matthias,
Polo Simona
Publication year - 2011
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2010.118
Subject(s) - biology , ubiquitin , microbiology and biotechnology , epidermal growth factor receptor , epidermal growth factor , deubiquitinating enzyme , endocytic cycle , signal transduction , skp1 , proteomics , transcription factor , ubiquitin ligase , cell signaling , biochemistry , receptor , gene , endocytosis
The activity, localization and fate of many cellular proteins are regulated through ubiquitination, a process whereby one or more ubiquitin (Ub) monomers or chains are covalently attached to target proteins. While Ub‐conjugated and Ub‐associated proteomes have been described, we lack a high‐resolution picture of the dynamics of ubiquitination in response to signaling. In this study, we describe the epidermal growth factor (EGF)‐regulated Ubiproteome, as obtained by two complementary purification strategies coupled to quantitative proteomics. Our results unveil the complex impact of growth factor signaling on Ub‐based intracellular networks to levels that extend well beyond what might have been expected. In addition to endocytic proteins, the EGF‐regulated Ubiproteome includes a large number of signaling proteins, ubiquitinating and deubiquitinating enzymes, transporters and proteins involved in translation and transcription. The Ub‐based signaling network appears to intersect both housekeeping and regulatory circuitries of cellular physiology. Finally, as proof of principle of the biological relevance of the EGF‐Ubiproteome, we demonstrated that EphA2 is a novel, downstream ubiquitinated target of epidermal growth factor receptor (EGFR), critically involved in EGFR biological responses.