PXD006648

PXD006648 is an original dataset announced via ProteomeXchange.

Title	Modulation of proteostasis counteracts oxidative stress and affects DNA base excision repair capacity in ATM-deficient cells
Description	Ataxia telangiectasia (A-T) is a syndrome associated with loss of ATM protein function. Neurodegeneration and cancer predisposition, both hallmarks of A-T, are likely to emerge as a consequence of the persistent oxidative stress and DNA damage observed in this disease. Surprisingly however, despite these severe features, a lack of functional ATM is still compatible with early life, suggesting that adaptation mechanisms contributing to cell survival must be in place. Here we address this gap in our knowledge by analysing the process of human fibroblast adaptation to the lack of ATM. We identify profound rearrangement in cellular proteostasis occurring very early on after loss of ATM in order to counter protein damage originating from oxidative stress. Change in proteostasis, however, is not without repercussions. Modulating protein turnover in ATM-depleted cells also has an adverse effect on the DNA base excision repair pathway, the major DNA repair system that deals with oxidative DNA damage. As a consequence, the burden of unrepaired endogenous DNA lesions intensifies, progressively leading to genomic instability. Our study provides a glimpse at the cellular consequences of loss of ATM and highlights a previously overlooked role for proteostasis in maintaining cell survival in the absence of ATM function.
HostingRepository	PRIDE
AnnounceDate	2017-09-04
AnnouncementXML	Submission_2017-09-04_03:25:33.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	iolanda Vendrell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2017-06-02 00:39:12	ID requested
⏵ 1	2017-09-04 03:25:34	announced

Subramanian K, Rauniyar N, Lavalle, é, -Adam M, Yates JR, Balch WE, Quantitative Analysis of the Proteome Response to the Histone Deacetylase Inhibitor (HDACi) Vorinostat in Niemann-Pick Type C1 disease. Mol Cell Proteomics, 16(11):1938-1957(2017) [pubmed]

curator keyword: Biological

submitter keyword: ataxia telangiectasia mutated, reactive oxygen species, protein synthesis, proteasome, base excision repair

Grigory L Dianov
contact affiliation	CRUK & MRC Oxford Institute for Radiation Oncology, University of Oxford, Department of Oncology, Old Road Campus Research Building, Oxford, OX37DQ, UK
contact email	grigory.dianov@oncology.ox.ac.uk
lab head
iolanda Vendrell
contact affiliation	CRUK-MRC Oxford Institute for Radiation Oncology, Oxford University
contact email	iolanda.vendrell@oncology.ox.ac.uk
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/2017/09/PXD006648

PRIDE project URI

• PRIDE
  1. PXD006648
     1. Label: PRIDE project
     2. Name: Modulation of proteostasis counteracts oxidative stress and affects DNA base excision repair capacity in ATM-deficient cells