PXD012559-1

PXD012559 is an original dataset announced via ProteomeXchange.

Title	Quantitative phosphoproteomics to unravel the cellular response to chemical stressors with different modes of action
Description	Cells activate various stress response pathways when exposed to chemicals that can damage cellular macromolecules and organelles. Whether different chemical stressors activate common and/or stressor-specific pathways and to what extent is largely unclear. Here, we used quantitative phosphoproteomics to compare the phosphorylation signaling cascades induced by four stressors with different modes of action: the DNA damaging agent: cisplatin (CDDP), the topoisomerase II inhibitor: etoposide (ETO), the pro-oxidant: diethyl maleate (DEM) and the immunosuppressant: cyclosporine A (CsA). We show that equitoxic doses of these stressors induce distinctive and complex phosphorylation signaling cascades. Our results reveal stressor-specific kinase motifs and pathways. CDDP activates the DNA damage response (DDR) predominantly through the replication-stress related Atr kinase, whereas ETO triggers the DDR through Atr as well as the DNA double stranded break associated Atm kinase. CsA shares with ETO, a strong activation of CK2 kinase and significant Atm phosphorylation but lacks prominent activation of the DDR. Congruent with their known modes of action, CsA-mediated signaling is related to down-regulation of pathways that control hematopoietic differentiation and immunity whereas oxidative stress is the most prominent initiator of DEM-modulated stress signaling. This study presents an unprecedented molecular insight into the activated phosphorylation signaling cascades after various types of stressors.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_10:30:44.882.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bharath Sampadi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	6x(13)C; 6x(13)C; (4,4,5,5-(2)H4)-L-lysine; phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; 6x(13)C labeled L-arginine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-29 07:52:38	ID requested
⏵ 1	2024-10-07 10:30:45	announced

10.1007/s00204-020-02712-7;

Sampadi B, Pines A, Munk S, Mi, š, ovic B, de Groot AJ, van de Water B, Olsen JV, Mullenders LHF, Vrieling H, Quantitative phosphoproteomics to unravel the cellular response to chemical stressors with different modes of action. Arch Toxicol, 94(5):1655-1671(2020) [pubmed]

curator keyword: Biological

submitter keyword: Phosphoproteomics, Topbp1, Mdc1, post-translational modification, mass spectrometry, CyclosporineA, Mouse,Biological, Phosphorylation, LC-MSMS, mESCs, Atr, Atm, SILAC, signal transduction, Diethylmaleate, Etoposide, Cisplatin, Rad51

Harry Vrieling
contact affiliation	DNA damage responses and cancer lab Department of Human Genetics Leiden University Medical Center Eithovenweg 20 2333ZC Leiden The Netherlands
contact email	h.vrieling@lumc.nl
lab head
Bharath Sampadi
contact affiliation	Leiden University Medical Center
contact email	b.k.sampadi@lumc.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/2020/03/PXD012559

PRIDE project URI

• PRIDE
  1. PXD012559
     1. Label: PRIDE project
     2. Name: Quantitative phosphoproteomics to unravel the cellular response to chemical stressors with different modes of action