The LUBAC participates to antigen receptor-mediated NF-κB activation and survival of lymphoma

To identify new elements of the CBM complex, we performed a mass spectrometr

y screen using the kinase CK1a as a bait. We found that the linear ubiquitin assembly complex (LUBAC, composed of the E3 ligases, HOIP and HOIL-1, and of SHARPIN), which was previously linked to cytokine-mediated NF-kB activation, dynamically integrates the CBM and marshals the optimal activation of NF-kB following antigen receptor ligation. Interestingly, the catalytic activity of the LUBAC is dispensable in this context. The LUBAC also participates to preassembled CBM complex in cells derived from ABC DLBCL. Silencing the LUBAC reduced NF-kB activation and was toxic in ABC DLBCL cell lines Altogether, these findings unveil the LUBAC as a new player during lymphocyte activation and in B cell lymphoma (Dubois SM et al. A catalytic-independent role for the LUBAC in NF-kB activation upon antigen receptor engagement and in lymphoma cells. Blood. 2014. Apr 3;123(14):2199-203.)