MassIVE MSV000080781

Imported Reanalysis Dataset Public PXD004181

HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B cell receptor signaling

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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. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: HSP90 ; Burkitt’s lymphoma ; BCR signaling ; Syk ; mass spectrometry ; phosphoproteomics

Contact

Principal Investigators:
(in alphabetical order) 		Henning Urlaub, 1. Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 G�ttingen, Germany 2. Bioanalytics, University Medical Center, Robert-Koch-Stra�e 40, 37075 G�ttingen, Germany, N/A
Submitting User: ccms

Publications

Walter R, Pan KT, Doebele C, Comoglio F, Tomska K, Bohnenberger H, Young RM, Jacobs L, Keller U, Bönig 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. 2017 Feb 2;129(5):598-608. Epub 2016 Nov 15.

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