PXD022707

PXD022707 is an original dataset announced via ProteomeXchange.

Title	Oncogene-dependent sloppiness in mRNA translation
Description	mRNA translation is a highly conserved and tightly-controlled mechanism for protein synthesis. However, despite protein quality control mechanisms, amino-acid shortage in melanoma induces aberrant proteins by ribosomal frameshifting. The extent and the underlying mechanisms related to this phenomenon are yet unknown. Here, we show that tryptophan-depletion-induced ribosomal frameshifting is a widespread phenomenon in cancer. We termed this event sloppiness and strikingly observed its association with MAPK pathway hyperactivation. Indeed, sloppiness is stimulated by RAS activation in primary cells, suppressed by pharmacological inhibition of the oncogenic MAPK pathway in sloppy cells, and is restored in cells with acquired resistance to MAPK pathway inhibition. Interestingly, sloppiness causes aberrant peptide presentation at the cell surface, allowing recognition and specific killing of drug-resistant cancer cells by T lymphocytes. Thus, while oncogenes empower cancer progression and aggressiveness, they also expose a vulnerability by provoking the production of aberrant peptides through sloppiness.
HostingRepository	PRIDE
AnnounceDate	2021-09-29
AnnouncementXML	Submission_2021-09-28_22:40:49.987.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 Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-24 07:56:27	ID requested
1	2021-09-28 05:25:37	announced
⏵ 2	2021-09-28 22:40:50	announced	2021-09-29: Updated project metadata.

10.1016/J.MOLCEL.2021.09.002;

Champagne J, Pataskar A, Blommaert N, Nagel R, Wernaart D, Ramalho S, Kenski J, Bleijerveld OB, Zaal EA, Berkers CR, Altelaar M, Peeper DS, Faller WJ, Agami R, Oncogene-dependent sloppiness in mRNA translation. Mol Cell, 81(22):4709-4721.e9(2021) [pubmed]

submitter keyword: ribosomal frameshifting, cancer, tryptophan depletion, immunoprecipitation,human, translation, LC-MS/MS

Reuven Agami
contact affiliation	Division of Oncogenomics, Oncode institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands
contact email	r.agami@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/2021/09/PXD022707

PRIDE project URI

• PRIDE
  1. PXD022707
     1. Label: PRIDE project
     2. Name: Oncogene-dependent sloppiness in mRNA translation