PXD044085

PXD044085 is an original dataset announced via ProteomeXchange.

Title	Chemotherapy-induced codon-specific immunopeptidome diversification
Description	Deregulated mRNA translation in cancer is a source of aberrant protein production when tryptophan shortage is induced by anti-tumor immunity (refs). Tryptophan is decoded by only one codon, and currently the consequences of aberrant protein production in conditions of a shortage of amino acids decoded by multiple codons are unknown. Leucine is decoded by six codons, and its levels influence a variety of key processes in cancer, including the control of mTOR signaling (ref) and epithelial to mesenchymal transition (PMID: 28274951). Here, we show that both leucine deprivation and DNA damage elicit ribosomal stalling and subsequent aberrant protein production predominantly at one codon for leucine, UUA. Mechanistically, we found that the leucine tRNA lowest in abundance is causative for ribosomal stalling and aberrant protein production. In addition, UUA-induced aberrant protein production impacts the landscape of neoepitopes presented at the surface of cancer cells, which can elicit T-cell recognition and killing. Altogether, codon-specific induction of neoepitopes by chemotherapy and leucine diet opens up new avenues for the development of adoptive T cell therapies.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_11:09:10.654.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	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-25 17:13:21	ID requested
⏵ 1	2025-05-06 11:09:11	announced

Kochavi A, Nagel R, K, ö, rner PR, Bleijerveld OB, Lin CP, Huinen Z, Malka Y, Proost N, van de Ven M, Feng X, Navarro JM, Pataskar A, Peeper DS, Champagne J, Agami R, Chemotherapeutic agents and leucine deprivation induce codon-biased aberrant protein production in cancer. Nucleic Acids Res, 52(22):13964-13979(2024) [pubmed]

10.1093/nar/gkae1110;

submitter keyword: aberrant protein,mRNA translation, tryptophan, leucine, ribosomal stalling, immunopeptidomics, neoepitopes

Onno B Bleijerveld
contact affiliation	The Netherlands Cancer Institute Proteomics Facility, Plesmanlaan 121, 1066CX, Amsterdam, The 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

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/2025/05/PXD044085

PRIDE project URI

• PRIDE
  1. PXD044085
     1. Label: PRIDE project
     2. Name: Chemotherapy-induced codon-specific immunopeptidome diversification