PXD004181-3

PXD004181 is an original dataset announced via ProteomeXchange.

Title	HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B cell receptor signaling
Description	Burkitt’s lymphoma (BL) is an aggressive B-cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Because of their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Hence, there is a need for targeted therapies. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We observed that, among other compounds, inhibitors of heat shock protein 90 (HSP90) induce apoptosis in BL cells in vitro at concentrations that did not affect normal B cells. By global proteomic and phosphoproteomic profiling, we found that in BL, HSP90 inhibition compromises activity of the pivotal B cell antigen receptor (BCR)-proximal effector spleen tyrosine kinase (SYK), which we identified as an HSP90 client protein. Consistently, expression of constitutively active TEL-SYK counteracted the apoptotic effect of HSP90 inhibition. Hence, our study provides a molecular rationale for the use of HSP90 inhibitors in the treatment of BL by demonstrating that HSP90 inhibition interferes with tonic BCR signaling and thus impairs BL cell survival.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:32:27.745.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kuan-Ting Pan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-05-18 06:08:55	ID requested
1	2017-01-02 05:09:22	announced
2	2017-01-18 05:14:43	announced	Updated publication reference for PubMed record(s): 28064214.
⏵ 3	2024-10-22 04:32:31	announced	2024-10-22: Updated project metadata.

Walter R, Pan KT, Doebele C, Comoglio F, Tomska K, Bohnenberger H, Young RM, Jacobs L, Keller U, B, ö, nig H, Engelke M, Rosenwald A, Urlaub H, Staudt LM, Serve H, Zenz T, Oellerich T, HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B-cell receptor signaling. Blood, 129(5):598-608(2017) [pubmed]

10.1182/blood-2016-06-721423;

curator keyword: Biomedical

submitter keyword: HSP90, Burkitt’s lymphoma , BCR signaling, mass spectrometry, Syk, phosphoproteomics

Henning Urlaub
contact affiliation	1. Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany 2. Bioanalytics, University Medical Center, Robert-Koch-Straße 40, 37075 Göttingen, Germany
contact email	henning.urlaub@mpibpc.mpg.de
lab head
Kuan-Ting Pan
contact affiliation	MPI for Biophysical Chemistry
contact email	kpan@mpibpc.mpg.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/PXD004181

PRIDE project URI

• PRIDE
  1. PXD004181
     1. Label: PRIDE project
     2. Name: HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B cell receptor signaling