PXD013541

PXD013541 is an original dataset announced via ProteomeXchange.

Title	proteomics analysis of LN308 cell line under treatment with tunicamycin and thapsigargin
Description	Accumulation of unfolded proteins in the endoplasmic reticulum triggers the unfolded protein response (UPR), an adaptive signal transduction pathway aimed at reinstating cellular homeostasis, or, if that fails, at triggering of apoptosis. The UPR plays a key role in a variety of disorders (including diabetes, neurodegenerative disorders, and inflammatory processes) and has been implicated in cancer progression and resistance to chemotherapy. However, the mechanisms and pathways by which the UPR contributes to chemoresistance are only poorly understood. We have employed a multi-omics approach to monitor changes to gene expression after induction of the UPR with two different compounds, probing in parallel the transcriptome, the proteome, and changes to translation. Stringent filtering reveals the induction of 267 genes (the UPR regulon), many of which have not previously been implicated in stress response pathways. We experimentally demonstrate that UPR-mediated translational control via phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2a) and subsequent induction of activating transcription factor 4 (ATF4) causes an up-regulation of enzymes involved in a pathway that diverts intermediate metabolites from glycolysis to fuel mitochondrial one-carbon metabolism. This metabolic rewiring of the cells results in resistance to treatment with the widely-used folate anti-metabolites Methotrexate and Permetrexed.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:30:04.577.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD013541
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Chi Nguyen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Ammonia-loss; Gln->pyro-Glu; Glu->pyro-Glu; Oxidation; Carbamidomethyl; Acetyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-17 05:29:26	ID requested
⏵ 1	2024-10-07 13:30:05	announced

10.6019/PXD013541;

10.1038/s41467-020-16747-y;

Reich S, Nguyen CDL, Has C, Steltgens S, Soni H, Coman C, Freyberg M, Bichler A, Seifert N, Conrad D, Knobbe-Thomsen CB, Tews B, Toedt G, Ahrends R, Medenbach J, A multi-omics analysis reveals the unfolded protein response regulon and stress-induced resistance to folate-based antimetabolites. Nat Commun, 11(1):2936(2020) [pubmed]

submitter keyword: glioblastoma,label-free, shot-gun proteomics, DDA

Robert Ahrends
contact affiliation	Lipidomics Group Leibniz-Institute for analytical science – ISAS – e.V. Otto-Hahn-Straße 6b 44227 Dortmund, Germany
contact email	robert.ahrends@isas.de
lab head
Chi Nguyen
contact affiliation	Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V. Bunsen-Kirchhoff-Straße 11 | 44139 Dortmund, Germany
contact email	chi.nguyen@isas.de
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/2020/05/PXD013541

PRIDE project URI

• PRIDE
  1. PXD013541
     1. Label: PRIDE project
     2. Name: proteomics analysis of LN308 cell line under treatment with tunicamycin and thapsigargin