PXD047709-1

PXD047709 is an original dataset announced via ProteomeXchange.

Title	Quantitative modelling of B cell signaling in aggressive B cell lymphoma
Description	The B cell receptor (BCR) signaling, required for the survival and maturation of B cells, is a major deregulated pathway in B cell lymphomas. Several mutations are known to enhance the tonic BCR signal in Burkitt lymphomas (BL) or to mimic an activated receptor in some diffuse large B cell lymphomas (DLBCL). While the proximal events and kinases of the BCR signaling are well studied, less is known about the interactions of downstream effector pathways. In order to reach a less abstract description of this pathway we decided to employ the Modular Response Analysis-based modelling approach STASNet on more directly connected phosphorylation data. Using a Luminex proteomics platform we measured the phosphorylation of fourteen signaling and effector proteins after activating the B cell receptor (BCR) signaling and/or using inhibitors directed against seven intracellular signaling molecules in two independent Burkitt lymphoma cells (BL-2, BL-41). Application of a novel two step STASNet modelling pipeline unveiled novel feedback and crosstalk structures in the BCR-driven signaling network, including a crosstalk from p38 which negatively regulates MEK/ERK-activity in the presence of active BCR. Using Western Blot measurements, we verified and further characterized the p38-MEK/ERK crosstalk and demonstrated that it is a general mechanism in BL cells. Global Tandem Mass Tag (TMT) phosphoproteomic analysis on BL-2 cells found PI3K to be a major mediator of B-cell receptor signaling and manifested the p38-ERK crosstalk directly on ERK phosphosites and indirectly on seven bona fide ERK targets. We also noticed that the BL-2-learned pathway network structure was transferable to perturbation data from closely related BL-41 cells. Moreover, - compared to a literature-derived network - the BL-2-developed predictive pathway proved also to be a better starting point for network development in cells with aberrant BCR signaling in two representative cell lines derived from Diffuse large B cells (HBL-1, OCI-LY3). This indicates that models trained on activated B-cells are highly informative to be transferred to closely related cancer signaling network.
HostingRepository	PRIDE
AnnounceDate	2024-09-14
AnnouncementXML	Submission_2024-09-14_09:11:11.190.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marieluise Kirchner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-11 07:08:52	ID requested
⏵ 1	2024-09-14 09:11:11	announced
2	2024-10-22 06:58:22	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: lymphoma, human, oncogenic signaling,STASNet

Philipp Mertins
contact affiliation	Core Unit Proteomics, Berlin Institute of Health at Charite - Universitaetsmedizin Berlin and Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany
contact email	philipp.mertins@mdc-berlin.de
lab head
Marieluise Kirchner
contact affiliation	Proteomics Platform, BIH@Charite
contact email	marieluise.kirchner@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047709
     1. Label: PRIDE project
     2. Name: Quantitative modelling of B cell signaling in aggressive B cell lymphoma