PXD074426

PXD074426 is an original dataset announced via ProteomeXchange.

Title	VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.
Description	Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. Here, we undertake genome-wide CRISPR/Cas9 screening to reveal synthetic lethal interactors of VHL, and uncover that loss of Core Binding Factor β (CBF-β) causes cell death in VHL-null ccRCC cell lines and impairs tumour establishment and growth in vivo. This synthetic relationship is independent of the elevated activity of hypoxia inducible factors (HIFs) in VHL-null cells, but does involve the RUNX transcription factors that are known binding partners of CBF-β. Mechanistically, CBF-β loss leads to upregulation of type I interferon signalling, and we uncover a direct inhibitory role for CBF-β at the STING locus controlling Interferon Stimulated Gene expression. Targeting CBF-β in kidney cancer both selectively induces tumour cell lethality and promotes activation of type I interferon signalling.
HostingRepository	PRIDE
AnnounceDate	2026-02-13
AnnouncementXML	Submission_2026-02-13_06:39:09.833.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD074426
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	James Williamson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-13 05:17:05	ID requested
⏵ 1	2026-02-13 06:39:10	announced

10.6019/PXD074426;

submitter keyword: STING, CBF-β,VHL, clear cell renal cell carcinoma, type I interferon

James Nathan
contact affiliation	Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, CB2 0AW, UK
contact email	jan33@cam.ac.uk
lab head
James Williamson
contact affiliation	University of Cambridge
contact email	jcw76@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD074426
     1. Label: PRIDE project
     2. Name: VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.