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PXD004816

PXD004816 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProtein abundance of AKT and ERK pathway components governs cell-type-specific regulation of proliferation
DescriptionSignaling through the AKT and ERK pathways controls cell proliferation. However, the integrated regulation of this multistep process, involving signal processing, cell growth and cell-cycle progression, is poorly understood. Here we study different murine hematopoietic cell types, in which AKT and ERK signaling is triggered by erythropoietin (Epo). Although these cell types share the molecular network topology for pro-proliferative Epo signaling, they exhibit distinct proliferative responses. Iterating quantitative experiments and mathematical modeling, we identify two molecular sources for cell-type-specific proliferation. First, cell-type-specific protein abundance patterns cause differential signal flow along the AKT and ERK pathways. Second, downstream regulators of both pathways have differential effects on proliferation, suggesting that protein synthesis is rate-limiting for faster-cycling cells while slower cell-cycles are controlled at the G1-S progression. The integrated mathematical model of Epo-driven proliferation explains cell-type-specific effects of targeted AKT and ERK inhibitors and faithfully predicts based on the protein abundance anti-proliferative effects of inhibitors in primary human erythroid progenitor cells. Our findings suggest that the effectiveness of targeted cancer therapy might become predictable from protein abundance patterns.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:32:22.257.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlexander Held
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-08-16 01:08:52ID requested
12017-01-30 03:56:52announced
22024-10-22 04:32:27announced2024-10-22: Updated project metadata.
Publication List
Adlung L, Kar S, Wagner MC, She B, Chakraborty S, Bao J, Lattermann S, Boerries M, Busch H, Wuchter P, Ho AD, Timmer J, Schilling M, H, ö, fer T, Klingm, ü, ller U, proliferation. Mol Syst Biol, 13(1):904(2017) [pubmed]
10.15252/msb.20167258;
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: Human, CFU-E, proteome ruler, label-free quantification
Contact List
Marcel Schilling
contact affiliationGerman Cancer Research Center (DKFZ)
contact emailm.schilling@dkfz.de
lab head
Alexander Held
contact affiliationDKFZ Heidelberg
contact emaila.gorol@dkfz.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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