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PXD030580-1

PXD030580 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleUBIQUITIN LIGASE STUB1 DESTABILIZES IFNγ-RECEPTOR COMPLEX TO SUPPRESS TUMOR IFNγ SIGNALING
DescriptionThe cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about 36 regulation of its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators of IFNγ-R1 cell surface abundance, we identified STUB1 as an E3 ubiquitin ligase for IFNγ-R1 in complex with its signal-relaying kinase JAK1. STUB1 mediates ubiquitination-dependent proteasomal degradation of IFNγ-R1/JAK1 complex through IFNγ-R1K285 and JAK1K249. Conversely, STUB1 inactivation amplifies IFNγ signaling, sensitizing tumor cells to cytotoxic T cells in vitro. This was corroborated by an anticorrelation between STUB1 expression and IFNγ response in ICB-treated patients. Consistent with the context-dependent effects of IFNγ in vivo, anti-PD-1 response was increased in heterogenous tumors comprising both wildtype and STUB1-deficient cells but not full STUB1 knockout tumors. These results uncover STUB1 as a critical regulator of IFNγ-R1, and highlight the context-dependency of STUB1-regulated IFNγ signaling for ICB outcome.
HostingRepositoryPRIDE
AnnounceDate2022-03-07
AnnouncementXMLSubmission_2022-03-07_07:21:54.453.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterOnno Bleijerveld
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListubiquitinylated lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480; Orbitrap Fusion ETD
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-12-21 12:31:30ID requested
12022-03-07 07:21:54announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: ubiquitination, melanoma, immune checkpoint blockade, IFNγ, STUB1
Contact List
Maarten Altelaar
contact affiliationNKI Proteomics Facility Plesmanlaan 121 1066CX Amsterdam, The Netherlands
contact emailm.altelaar@nki.nl
lab head
Onno Bleijerveld
contact affiliationThe Netherlands Cancer Institute
contact emailo.bleijerveld@nki.nl
dataset submitter
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Dataset FTP location
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