PXD030580 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | UBIQUITIN LIGASE STUB1 DESTABILIZES IFNγ-RECEPTOR COMPLEX TO SUPPRESS TUMOR IFNγ SIGNALING |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-03-07 |
AnnouncementXML | Submission_2022-03-07_07:21:54.453.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Onno Bleijerveld |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | ubiquitinylated lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480; Orbitrap Fusion ETD |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-12-21 12:31:30 | ID requested | |
⏵ 1 | 2022-03-07 07:21:54 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: ubiquitination, melanoma, immune checkpoint blockade, IFNγ, STUB1 |
Contact List
Maarten Altelaar |
contact affiliation | NKI Proteomics Facility Plesmanlaan 121 1066CX Amsterdam, The Netherlands |
contact email | m.altelaar@nki.nl |
lab head | |
Onno Bleijerveld |
contact affiliation | The Netherlands Cancer Institute |
contact email | o.bleijerveld@nki.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD030580
- Label: PRIDE project
- Name: UBIQUITIN LIGASE STUB1 DESTABILIZES IFNγ-RECEPTOR COMPLEX TO SUPPRESS TUMOR IFNγ SIGNALING