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PXD026103

PXD026103 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeted mass spectrometry enables quantification of novel pharmacodynamic biomarkers of ATM kinase inhibitors
DescriptionATM is a serine/threonine protein kinase that is responsible for initiation of DNA repair of double-stranded breaks and is a therapeutic target in cancer. A lack of analytically robust and multiplexed assays has hampered mechanistic studies of action and determination of optimal, robust pharmacodynamic biomarkers for clinical development of new therapies targeting ATM. Targeted mass spectrometry-based assays have been shown to be capable of enabling quantitative phosphosignaling studies and identification of novel phosphorylation sites. To identify new pharmacodynamic markers of ATM inhibition and expand the capabilities of targeted proteomics for quantitative profiling of the DNA damage response, we developed and fully analytically characterized a 51-plex assay quantifying protein expression and post-translational modification (phosphorylation) following induction of DNA damage. The linear range was over 3 orders of magnitude, the median inter-assay variability was 11% CV, and the assay is capable of being used in conjunction with other multiple reaction monitoring-based multiplexed assay panels. Proof-of-principle studies quantify signaling following DNA damage (ionizing radiation) in immortalized cell lines and primary human cells, identifying NUMA1 pS395 as a PD marker for ATM inhibition following DNA damage. Furthermore, the study shows the utility of using a quantitative multiplexed assay for studying cellular signaling dynamics, and the potential application to pharmacodynamic and mechanism of action studies, including development of new pharmacodynamic markers for clinical application.
HostingRepositoryPRIDE
AnnounceDate2021-07-29
AnnouncementXMLSubmission_2021-07-29_03:04:04.353.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJacob Kennedy
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListcarbamoylated residue; phosphorylated residue; isotope labeled residue; 6x(13)C labeled residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-05-19 22:40:03ID requested
12021-07-29 03:04:04announced
Publication List
Dataset with its publication pending
Keyword List
ProteomeXchange project tag: CPTAC Consortium
submitter keyword: Human, Lymphoblast, ATM, phosphorylation
Contact List
Amanda Paulovich
contact affiliationClinical Research Division, Fred Hutchinson Cancer Research Center
contact emailapaulovi@fredhutch.org
lab head
Jacob Kennedy
contact affiliationFred Hutchinson Cancer Research Center
contact emailjkennedy@fhcrc.org
dataset submitter
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Dataset FTP location
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