Abstract:
:Ubiquitin is post-translationally modified by phosphorylation at several sites, but the consequences of these modifications are largely unknown. Here, we synthesize multi-milligram quantities of ubiquitin phosphorylated at serine 20, serine 57, and serine 65 via genetic code expansion. We use these phosphoubiquitins for the enzymatic assembly of 20 isomeric phosphoubiquitin dimers, with different sites of isopeptide linkage and/or phosphorylation. We discover that phosphorylation of serine 20 on ubiquitin converts UBE3C from a dual-specificity E3 ligase into a ligase that primarily synthesizes K48 chains. We profile the activity of 31 deubiquitinases on the isomeric phosphoubiquitin dimers in 837 reactions, and we discover that phosphorylation at distinct sites in ubiquitin can activate or repress cleavage of a particular linkage by deubiquitinases and that phosphorylation at a single site in ubiquitin can control the specificity of deubiquitinases for distinct ubiquitin linkages.
journal_name
Cell Repjournal_title
Cell reportsauthors
Huguenin-Dezot N,De Cesare V,Peltier J,Knebel A,Kristaryianto YA,Rogerson DT,Kulathu Y,Trost M,Chin JWdoi
10.1016/j.celrep.2016.06.064subject
Has Abstractpub_date
2016-07-26 00:00:00pages
1180-1193issue
4issn
2211-1247pii
S2211-1247(16)30818-Xjournal_volume
16pub_type
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