PXD062296-1

PXD062296 is an original dataset announced via ProteomeXchange.

Title	SPOP mislocalisation drives mis-splicing and depletion of MHC class I and TFEB in cancer
Description	Nuclear speckle-type POZ protein (SPOP) is the most commonly point-mutated gene in prostate adenocarcinoma, and mislocalises to the cytoplasm in clear cell renal cell carcinoma (ccRCC) with von Hippel Lindau (VHL) loss. SPOP was hitherto characterised as an E3 ubiquitin ligase adaptor. Here, we find that SPOP plays a non-canonical role as a scaffold for RNA-binding proteins within the nuclear speckle, and that speckles lacking competent SPOP exhibit compromised hypoxia- and nutrient-sensitive splicing. This causes nonsense-mediated decay of intron-retaining transcripts from the major histocompatibility complex (MHC) class I locus, and from the master autophagy regulator, transcription factor EB (TFEB), the downregulation of which is associated with worse human ccRCC patient survival. We therefore reveal a dual, compartment-specific role for SPOP in carcinogenesis. While cytoplasmic SPOP is oncogenic, we find that nuclear SPOP has a tumour-suppressive splicing function impacting immune surveillance and autophagy that is lost upon its mislocalisation or mutation.
HostingRepository	PRIDE
AnnounceDate	2026-01-07
AnnouncementXML	Submission_2026-01-07_02:58:32.953.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robin Antrobus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-27 01:34:04	ID requested
⏵ 1	2026-01-07 02:58:33	announced

Dataset with its publication pending

submitter keyword: nutrient-sensitive, cancer,RNA-binding

Prof. David C. Rubinsztein
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
contact email	dcr1000@cam.ac.uk
lab head
Robin Antrobus
contact affiliation	CIMR medicine
contact email	pra29@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062296
     1. Label: PRIDE project
     2. Name: SPOP mislocalisation drives mis-splicing and depletion of MHC class I and TFEB in cancer