PXD028393-1

PXD028393 is an original dataset announced via ProteomeXchange.

Title	THE PHARMACOLOGICAL RESCUE OF CFTR BY LUMACAFTOR (VX-809) IN THE CYSTIC FIBROSIS BRONCHIAL EPITHELIUM IS ASSOCIATED WITH AN EXTENSIVE REORGANIZATION OF MITOCHONDRIA.
Description	Cystic Fibrosis (CF) is a genetic disorder CF is caused by mutations of the gene encoding for the cystic fibrosis transmembrane conductance regulator protein (CFTR), a transmembrane anion channel expressed at the apical membrane of several organs, including the epithelial cells of the airway. CFTR mutations result in dysfunctional ion transport across the apical membrane at the surface of the epithelia, generating thickened and dehydrated secretions. In the lung, this leads to a decrease in the mucociliary clearance, favoring bacterial colonization and progressive obstruction of the duct. Although over 2000 CFTR variants have been identified so far, the most common mutation is a deletion of the phenylalanine in position 508 (F508del), which shows an allelic frequency of around 90% among CF patients. F508del-CFTR is incorrectly folded, causing its retention at the endoplasmic reticulum (ER) and subsequent proteasomal degradation. Among the several drugs available in CF pharmacological treatment, VX-809 (commercial name Lumacaftor) is the most used drug for patients carrying F508del-CFTR mutation. This drug corrects the aberrant folding of F508del-CFTR by favoring the correct intramolecular interactions, thus enabling a higher number of copies of the defective protein to reach the plasma membrane. Localization of Organelle Proteins by Isotope Tagging after Differential ultra-Centrifugation (LOPIT-DC, https://doi.org/10.1038/s41467-018-08191-w) workflow was used to study the spatial localization of proteins in the CFBE41o- cells and how it is impacted by CFTR rescue triggered by VX-809. LOPIT-DC is a powerful and well-established tool for the investigation of the spatial distribution of global proteome within cells, which combines subcellular fractionation based on differential centrifugation, quantitative mass spectrometry, and machine learning. Its application provides a global snapshot of the steady-state subcelluler distribution of proteins. The aim of this project is to identify proteins that change their cellular localization in association with the treatment, to uncover molecules that play a role in the trafficking of the defective CFTR to the plasma membrane.
HostingRepository	PRIDE
AnnounceDate	2022-08-11
AnnouncementXML	Submission_2022-08-11_12:10:46.167.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Clarissa Braccia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:35:12	ID requested
⏵ 1	2022-08-11 12:10:46	announced

Braccia C, Christopher JA, Crook OM, Breckels LM, Queiroz RML, Liessi N, Tomati V, Capurro V, Bandiera T, Baldassari S, Pedemonte N, Lilley KS, Armirotti A, CFTR Rescue by Lumacaftor (VX-809) Induces an Extensive Reorganization of Mitochondria in the Cystic Fibrosis Bronchial Epithelium. Cells, 11(12):(2022) [pubmed]

submitter keyword: LOPIT-DC, Spatial proteomics, Cystic Fibrosis, CFBE41o- cells, VX-809

Kathryn S. Lilley
contact affiliation	Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK
contact email	k.s.lilley@bioc.cam.ac.uk
lab head
Clarissa Braccia
contact affiliation	Istituto Italiano di Tecnologia
contact email	clarissa.braccia@iit.it
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/2022/08/PXD028393

PRIDE project URI

• PRIDE
  1. PXD028393
     1. Label: PRIDE project
     2. Name: THE PHARMACOLOGICAL RESCUE OF CFTR BY LUMACAFTOR (VX-809) IN THE CYSTIC FIBROSIS BRONCHIAL EPITHELIUM IS ASSOCIATED WITH AN EXTENSIVE REORGANIZATION OF MITOCHONDRIA.