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

• Verfasst von: Corso, Jasmin [VerfasserIn]
• Verfasst von: Słabicki, Mikołaj [VerfasserIn]
• Verfasst von: Hüllein, Jennifer [VerfasserIn]
• Verfasst von: Zenz, Thorsten [VerfasserIn]
• Titel: Elucidation of tonic and activated B-cell receptor signaling in Burkitt’s lymphoma provides insights into regulation of cell survival
• Verf.angabe: Jasmin Corso, Kuan-Ting Pan, Roland Walter, Carmen Doebele, Sebastian Mohr, Hanibal Bohnenberger, Philipp Ströbel, Christof Lenz, Mikolaj Slabicki, Jennifer Hüllein, Federico Comoglio, Michael A. Rieger, Thorsten Zenz, Jürgen Wienands, Michael Engelke, Hubert Serve, Henning Urlaub, and Thomas Oellerich
• E-Jahr: 2016
• Jahr: May 6, 2016
• Umfang: 6 S.
• Fussnoten: Gesehen am 10.09.2019
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2016
• Band/Heft Quelle: 113(2016), 20, Seite 5688-5693
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.1601053113
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: B-cell receptor
• Sach-SW: cancer biology
• Sach-SW: lymphoma
• Sach-SW: phosphoproteome
• K10plus-PPN: 1676403299

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.