PXD030580-1

PXD030580 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-21 12:31:30	ID requested
⏵ 1	2022-03-07 07:21:54	announced

Dataset with its publication pending

submitter keyword: ubiquitination, melanoma, immune checkpoint blockade, IFNγ, STUB1

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/03/PXD030580

PRIDE project URI

• PRIDE
  1. PXD030580
     1. Label: PRIDE project
     2. Name: UBIQUITIN LIGASE STUB1 DESTABILIZES IFNγ-RECEPTOR COMPLEX TO SUPPRESS TUMOR IFNγ SIGNALING