PXD004816 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Protein abundance of AKT and ERK pathway components governs cell-type-specific regulation of proliferation |
Description | Signaling 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:32:22.257.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Alexander Held |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2016-08-16 01:08:52 | ID requested | |
1 | 2017-01-30 03:56:52 | announced | |
⏵ 2 | 2024-10-22 04:32:27 | announced | 2024-10-22: 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 affiliation | German Cancer Research Center (DKFZ) |
contact email | m.schilling@dkfz.de |
lab head | |
Alexander Held |
contact affiliation | DKFZ Heidelberg |
contact email | a.gorol@dkfz.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD004816
- Label: PRIDE project
- Name: Protein abundance of AKT and ERK pathway components governs cell-type-specific regulation of proliferation