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PXD026791 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRegulation of CYLD activity and specificity by phosphorylation and ubiquitin-binding CAP-Gly domains
DescriptionNon-degradative ubiquitin chains and phosphorylation events govern signaling responses by innate immune receptors. The deubiquitinase CYLD in complex with SPATA2 is recruited to receptor signaling complexes by the ubiquitin ligase LUBAC and regulates Met1- and Lys63-linked polyubiquitin and receptor signaling outcomes. Here, we investigated the molecular determinants of CYLD activity. We reveal that two CAP-Gly domains in CYLD are ubiquitin binding domains and demonstrate a requirement of CAP-Gly3 for CYLD activity and regulation of immune receptor signaling. Moreover, we identify a phosphorylation switch outside of the catalytic USP domain, which activates CYLD selectively towards Lys63-linked polyubiquitin. The phosphorylated residue Ser568 is a novel TNF-regulated phosphorylation site in CYLD and works in concert with Ser418 to enable CYLD-mediated deubiquitination and immune receptor signaling. We propose that phosphorylated CYLD together with SPATA2 and LUBAC functions as a ubiquitin-editing complex that rebalances Lys63- and Met1-linked polyubiquitin at receptor signaling complexes, resulting in escalated LUBAC signaling.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterGeorgina Berridge
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-06-18 03:51:13ID requested
12021-11-02 03:59:52announced
Publication List
Elliott PR, Leske D, Wagstaff J, Schlicher L, Berridge G, Maslen S, Timmermann F, Ma B, Fischer R, Freund SMV, Komander D, Gyrd-Hansen M, Regulation of CYLD activity and specificity by phosphorylation and ubiquitin-binding CAP-Gly domains. Cell Rep, 37(1):109777(2021) [pubmed]
Keyword List
submitter keyword: CYLD phosphorylation and Ub-binding
Contact List
Roman Fischer
contact affiliationDiscovery Proteomics Facitility, Target Discovery Institute, University of Oxford
contact emailroman.fischer@ndm.ox.ac.uk
lab head
Georgina Berridge
contact affiliationUniversity of Oxford
contact emailgeorgina.berridge@ndm.ox.ac.uk
dataset submitter
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