Oncogenic CARMA1 couples NF-κB and β-catenin signaling in diffuse large B-cell lymphomas

Oncogene
Miriam BognarDaniel Krappmann

Abstract

Constitutive activation of the antiapoptotic nuclear factor-κB (NF-κB) signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL). Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 in the NF-κB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of β-catenin and its destruction complex consisting of APC, AXIN1, CK1α and GSK3β to oncogenic CARMA1. Recruitment of the β-catenin destruction complex was independent of CARMA1-BCL10-MALT1 complex formation or constitutive NF-κB activation and promoted the stabilization of β-catenin. The β-catenin destruction complex was also recruited to CARMA1 in ABC DLBCL cell lines, which coincided with elevated β-catenin expression. In line, β-catenin was frequently detected in non-GCB DLBCL biopsies that rely on chronic BCR signaling. Increased β-catenin amounts alone were not sufficient to induce classical WNT target ...Continue Reading

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Citations

Oct 8, 2016·Frontiers in Immunology·Bin Ma, Michael O Hottiger
Dec 14, 2019·Nature Communications·Christine QuachChengyu Liang
Jul 16, 2016·Biological Chemistry·Isabel Meininger, Daniel Krappmann
Jul 22, 2016·Signal Transduction and Targeted Therapy·Wenzhi ShenRong Xiang
Feb 6, 2020·Anti-cancer Agents in Medicinal Chemistry·Feifei SunXin Wang
Jun 17, 2018·Journal of Hematology & Oncology·Swathi BalajiMichael Wang
Nov 30, 2019·Hematological Oncology·Francesco PiazzaGianpietro Semenzato
Mar 30, 2020·Nature Communications·Hao ZuoYihong Wan

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Datasets Mentioned

BETA
GSE70025

Methods Mentioned

BETA
fluorescence-activated cell sorting
affinity purification
co-immunoprecipitation
pull-down
co-IP
co-IPs
biopsies
PCR
enzyme-linked immunosorbent assay
PMA

Software Mentioned

FlowJo

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