A catalytic-independent role for the LUBAC in NF-κB activation upon antigen receptor engagement and in lymphoma cells. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Blood Année : 2014

A catalytic-independent role for the LUBAC in NF-κB activation upon antigen receptor engagement and in lymphoma cells.

Héloïse Leclair
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Thierry Fest
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Julie Gavard

Résumé

Antigen receptor-mediated nuclear factor κB (NF-κB) activation relies on the formation of a large multi-protein complex that contains CARMA1, BCL10, and MALT1 (CBM complex). This signalosome is pirated in the activated B-cell-like subgroup of diffuse large B-cell lymphoma (ABC DLBCL) to drive aberrant NF-κB activation, thereby promoting cell survival and propagation. Using an unbiased proteomic approach, we screened for additional components of the CBM in lymphocytes. We found that the linear ubiquitin chain assembly complex (LUBAC), which was previously linked to cytokine-mediated NF-κB activation, dynamically integrates the CBM and marshals NF-κB optimal activation following antigen receptor ligation independently of its catalytic activity. The LUBAC also participates in preassembled CBM complex in cells derived from ABC DLBCL. Silencing the LUBAC reduced NF-κB activation and was toxic in ABC DLBCL cell lines. Thus, our findings reveal a role for the LUBAC during lymphocyte activation and in B-cell malignancy.

Dates et versions

hal-00974733 , version 1 (07-04-2014)

Identifiants

Citer

Sonia Dubois, Catherine Alexia, Youtong Wu, Héloïse Leclair, Claire Leveau, et al.. A catalytic-independent role for the LUBAC in NF-κB activation upon antigen receptor engagement and in lymphoma cells.. Blood, 2014, 123 (14), pp.2199-203. ⟨10.1182/blood-2013-05-504019⟩. ⟨hal-00974733⟩
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