Proteomics

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

ABSTRACT: B-cell receptor (BCR) signaling promotes the survival of malignant B cells, such as Burkitt’s lymphoma (BL) and the activated B-cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). In contrast to ABC DLBCL, where malignant cells require chronic activation of the BCR for their survival, BL cells are dependent on tonic BCR signaling that is antigen-independent. Elucidation and systematic comparison of tonic and activated BCR signaling led to the identification of novel signaling effectors, among them ACTN4 and ARFGEF2, which were identified as regulators of BL cell survival. As tonic and activated BCR signaling are relevant for important aspects of B cell biology, our study helps in gaining an understanding of BCR-induced processes not only in malignant but potentially also physiological settings.

INSTRUMENT(S): LTQ Orbitrap Velos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Suspension Culture

DISEASE(S): Lymphoma

SUBMITTER: Kuan-Ting Pan  

LAB HEAD: Henning Urlaub

PROVIDER: PXD003492 | Pride | 2016-05-09

REPOSITORIES: Pride

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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 Jasmin J   Pan Kuan-Ting KT   Walter Roland R   Doebele Carmen C   Mohr Sebastian S   Bohnenberger Hanibal H   Ströbel Philipp P   Lenz Christof C   Slabicki Mikolaj M   Hüllein Jennifer J   Comoglio Federico F   Rieger Michael A MA   Zenz Thorsten T   Wienands Jürgen J   Engelke Michael M   Serve Hubert H   Urlaub Henning H   Oellerich Thomas T  

Proceedings of the National Academy of Sciences of the United States of America 20160506 20

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  ...[more]

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