PXD068912

PXD068912 is an original dataset announced via ProteomeXchange.

Title	Arginine deprivation of ASS1-deficient cancers drives mistranslation and shared neoepitope production
Description	Arginine biosynthesis is frequently suppressed in human cancer due to loss of argininosuccinate synthetase 1 (ASS1) expression, rendering cancer cells reliant on extracellular arginine. This observation propelled the development of systemic arginine depletion strategies, which are clinically safe but showed limited efficacy. Here, we show that in conditions of arginine scarcity, cancer cells with low ASS1 expression resort to aberrant mRNA translation in the form of ribosomal frameshifts and amino acid misincorporations. While aberrant proteins originated from most arginine codons, the predominant effect was observed at AGA. This codon-preference is caused by a selective decrease of tRNAArg(UCU) levels after arginine deprivation, which is linked to METTL1-mediated tRNA-modification. Using proteomics and immunopeptidomics, we validated that arginine shortage induces aberrant protein and neoepitope production at the endogenous level.
HostingRepository	PRIDE
AnnounceDate	2026-04-28
AnnouncementXML	Submission_2026-04-28_10:19:07.458.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: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-28 16:41:16	ID requested
⏵ 1	2026-04-28 10:19:08	announced

Dataset with its publication pending

submitter keyword: None

Onno Bleijerveld
contact affiliation	Netherlands Cancer Institute Proteomics Facility
contact email	o.bleijerveld@nki.nl
lab head
Onno Bleijerveld
contact affiliation	The Netherlands Cancer Institute
contact email	o.bleijerveld@nki.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068912
     1. Label: PRIDE project
     2. Name: Arginine deprivation of ASS1-deficient cancers drives mistranslation and shared neoepitope production