PXD026791 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Regulation of CYLD activity and specificity by phosphorylation and ubiquitin-binding CAP-Gly domains |
Description | Non-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. |
HostingRepository | PRIDE |
AnnounceDate | 2021-11-02 |
AnnouncementXML | Submission_2021-11-02_03:59:52.000.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD026791 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Georgina Berridge |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-06-18 03:51:13 | ID requested | |
⏵ 1 | 2021-11-02 03:59:52 | announced | |
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 affiliation | Discovery Proteomics Facitility, Target Discovery Institute, University of Oxford |
contact email | roman.fischer@ndm.ox.ac.uk |
lab head | |
Georgina Berridge |
contact affiliation | University of Oxford |
contact email | georgina.berridge@ndm.ox.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD026791
- Label: PRIDE project
- Name: Regulation of CYLD activity and specificity by phosphorylation and ubiquitin-binding CAP-Gly domains