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  Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival.

Corso, J., Pan, K. T., Walter, R., Doebele, C., Mohr, S., Bohnenberger, H., et al. (2016). Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival. Proceedings of the National Academy of Sciences of the United States of America, 113(20), 5688-5693. doi:10.1073/pnas.1601053113.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-5AA7-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-A029-0
Genre: Journal Article

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 Creators:
Corso, J.1, Author              
Pan, K. T.1, Author              
Walter, R., Author
Doebele, C., Author
Mohr, S., Author
Bohnenberger, H., Author
Ströbel, P., Author
Lenz, C.1, Author              
Slabicki, M., Author
Hüllein, J., Author
Comoglio, F., Author
Rieger, M. A., Author
Zenz, T., Author
Wienands, J., Author
Engelke, M., Author
Serve, H., Author
Urlaub, H.1, Author              
Oellerich, T., Author
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              

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Free keywords: B-cell receptor; cancer biology; lymphoma; phosphoproteome
 Abstract: Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified ∼16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments.

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Language(s): eng - English
 Dates: 2016-05-06
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1073/pnas.1601053113
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Title: Proceedings of the National Academy of Sciences of the United States of America
Source Genre: Journal
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Pages: - Volume / Issue: 113 (20) Sequence Number: - Start / End Page: 5688 - 5693 Identifier: -