PXD060710-1

PXD060710 is an original dataset announced via ProteomeXchange.

Title	Global and specific mechanisms stimulate mistranslation in cancer
Description	In the context of anti-tumor immunity, activated T cells secrete interferon-gamma (IFNγ) to induce indoleamine 2,3-dioxygenase (IDO1) in the target cancer cells. High IDO1 levels deplete tryptophan, leading to aberrant protein production due to tryptophan to phenylalanine codon reassignments (W>F substitutants) by tRNA misacylation1. Whether the generation of W>F substitutants is a controlled process contributing to cancer cell survival is unknown. Here, we set up a functional genetic screening approach to underpin the underlying mechanism of W>F substitutants. This has uncovered FTSJ1, an enzyme that 2’-O-methylates several tRNAs at positions 32 and 34 of their anticodon loop2. We show that FTSJ1 is highly expressed in cancer proteomes and that FTSJ1-mediated tRNAtrp modifications are required for the efficient production of W>F substitutants in the proteome and immunopeptidome of cancer cells. Functionally, FTSJ1 expression both stimulated cancer cell adaptability to IFNγ-mediated tryptophan shortage and induced T-cell activity against W>F neoepitopes. Thus, aberrant protein production is a regulated process with consequences for cell adaptation following stress.
HostingRepository	PRIDE
AnnounceDate	2026-09-04
AnnouncementXML	Submission_2026-09-04_01:53:19.570.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

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-12 00:10:05	ID requested
⏵ 1	2026-09-04 01:53:20	announced

Dataset with its publication pending

submitter keyword: LC-MSMS, anti-tumor immunity, W>F substitutants,FTSJ1, neo-epitopes

Onno Bleijerveld
contact affiliation	Mass Spectrometry/Proteomics Facility, Netherlands Cancer Institute, Amsterdam, Netherlands.
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. PXD060710
     1. Label: PRIDE project
     2. Name: Global and specific mechanisms stimulate mistranslation in cancer