PXD004816

PXD004816 is an original dataset announced via ProteomeXchange.

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

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.

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;

curator keyword: Biological, Biomedical

submitter keyword: Human, CFU-E, proteome ruler, label-free quantification

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

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/2017/01/PXD004816

PRIDE project URI

• PRIDE
  1. PXD004816
     1. Label: PRIDE project
     2. Name: Protein abundance of AKT and ERK pathway components governs cell-type-specific regulation of proliferation