Abstract:
:Ubiquitination is a post-translational modification (PTM) that is essential for balancing numerous physiological processes. To enable delineation of protein ubiquitination at a site-specific level, we generated an antibody, denoted UbiSite, recognizing the C-terminal 13 amino acids of ubiquitin, which remain attached to modified peptides after proteolytic digestion with the endoproteinase LysC. Notably, UbiSite is specific to ubiquitin. Furthermore, besides ubiquitination on lysine residues, protein N-terminal ubiquitination is readily detected as well. By combining UbiSite enrichment with sequential LysC and trypsin digestion and high-accuracy MS, we identified over 63,000 unique ubiquitination sites on 9,200 proteins in two human cell lines. In addition to uncovering widespread involvement of this PTM in all cellular aspects, the analyses reveal an inverse association between protein N-terminal ubiquitination and acetylation, as well as a complete lack of correlation between changes in protein abundance and alterations in ubiquitination sites upon proteasome inhibition.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Akimov V,Barrio-Hernandez I,Hansen SVF,Hallenborg P,Pedersen AK,Bekker-Jensen DB,Puglia M,Christensen SDK,Vanselow JT,Nielsen MM,Kratchmarova I,Kelstrup CD,Olsen JV,Blagoev Bdoi
10.1038/s41594-018-0084-ysubject
Has Abstractpub_date
2018-07-01 00:00:00pages
631-640issue
7eissn
1545-9993issn
1545-9985pii
10.1038/s41594-018-0084-yjournal_volume
25pub_type
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