NFIL3 contributes to cytotoxic T lymphocyte-mediated killing.

Cytotoxic T lymphocytes (CTLs) are key effectors of the adaptive immune system that recognize and eliminate virally infected and cancerous cells. In naive CD8 T cells, T-cell receptor (TCR) engagement drives a number of transcriptional, translational and proliferation changes over the course of hours and days leading to differentiation into CTLs. To gain a better insight into this mechanism, we compared the transcriptional profiles of naive CD8 T cells to those of activated CTLs.

Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma.

Extracellular vesicles (EVs) are lipid-based nanosized particles that convey biological material from donor to recipient cells. EVs play key roles in glioblastoma progression because glioblastoma stem-like cells (GSCs) release pro-oncogenic, pro-angiogenic, and pro-inflammatory EVs. However, the molecular basis of EV release remains poorly understood.

Teasing out function from morphology: Similarities between primary cilia and immune synapses.

Immune synapses are formed between immune cells to facilitate communication and coordinate the immune response. The reorganization of receptors involved in recognition and signaling creates a transient area of plasma membrane specialized in signaling and polarized secretion. Studies on the formation of the immune synapse between cytotoxic T lymphocytes (CTLs) and their targets uncovered a critical role for centrosome polarization in CTL function and suggested a striking parallel between the synapse and primary cilium.

Cytoskeletal control of the secretory immune synapse.

The immune synapse is a very important but often transient site for secretion between immune cells. How secretion is controlled in a coordinated fashion at the synapse is a subject of much investigation. Two key mechanisms are the polarisation of the centrosome and rapid actin dynamics across the immune synapses that form between interacting immune cells.

Serine 165 phosphorylation of SHARPIN regulates the activation of NF-κB.

The adaptor SHARPIN composes, together with the E3 ligases HOIP and HOIL1, the linear ubiquitin chain assembly complex (LUBAC). This enzymatic complex catalyzes and stamps atypical linear ubiquitin chains onto substrates to modify their fate and has been linked to the regulation of the NF-κB pathway downstream of most immunoreceptors, inflammation, and cell death. However, how this signaling complex is regulated is not fully understood.

The LUBAC participates in lysophosphatidic acid-induced NF-κB activation.

The natural bioactive glycerophospholipid lysophosphatidic acid (LPA) binds to its cognate G protein-coupled receptors (GPCRs) on the cell surface to promote the activation of several transcription factors, including NF-κB. LPA-mediated activation of NF-κB relies on the formation of a signalosome that contains the scaffold CARMA3, the adaptor BCL10 and the paracaspase MALT1 (CBM complex). The CBM complex has been extensively studied in lymphocytes, where it links antigen receptors to NF-κB activation via the recruitment of the linear ubiquitin assembly complex (LUBAC), a tripartite complex of HOIP, HOIL1 and SHARPIN.

Paracaspase MALT1 regulates glioma cell survival by controlling endo-lysosome homeostasis.

Glioblastoma is one of the most lethal forms of adult cancer with a median survival of around 15 months. A potential treatment strategy involves targeting glioblastoma stem-like cells (GSC), which constitute a cell autonomous reservoir of aberrant cells able to initiate, maintain, and repopulate the tumor mass. Here, we report that the expression of the paracaspase mucosa-associated lymphoid tissue l (MALT1), a protease previously linked to antigen receptor-mediated NF-κB activation and B-cell lymphoma survival, inversely correlates with patient probability of survival.

Pannexin-1 limits the production of proinflammatory cytokines during necroptosis.

The activation of mixed lineage kinase-like (MLKL) by receptor-interacting protein kinase-3 (RIPK3) controls the execution of necroptosis, a regulated form of necrosis that occurs in apoptosis-deficient conditions. Active oligomerized MLKL triggers the exposure of phosphatidylserine residues on the cell surface and disrupts the plasma membrane integrity by forming lytic pores. MLKL also governs endosomal trafficking and biogenesis of small extracellular vesicles as well as the production of proinflammatory cytokines during the early steps of necroptosis; however, the molecular basis continues to be elucidated.

CYLD Regulates Centriolar Satellites Proteostasis by Counteracting the E3 Ligase MIB1.

The tumor suppressor CYLD is a deubiquitinating enzyme that removes non-degradative ubiquitin linkages bound to a variety of signal transduction adaptors. CYLD participates in the formation of primary cilia, a microtubule-based structure that protrudes from the cell body to act as a "sensing antenna." Yet, how exactly CYLD regulates ciliogenesis is not fully understood.

Post-translational Modifications of the CARMA1-BCL10-MALT1 Complex in Lymphocytes and Activated B-Cell Like Subtype of Diffuse Large B-Cell Lymphoma.

Piracy of the NF-κB transcription factors signaling pathway, to sustain its activity, is a mechanism often deployed in B-cell lymphoma to promote unlimited growth and survival. The aggressive activated B-cell like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) exploits a multi-protein complex of CARMA1, BCL10, and MALT1 (CBM complex), which normally conveys NF-κB signaling upon antigen receptors engagement. Once assembled, the CBM also unleashes MALT1 protease activity to finely tune the immune response.

The paracaspase MALT1 cleaves the LUBAC subunit HOIL1 during antigen receptor signaling.

Antigen-receptor-mediated activation of lymphocytes relies on a signalosome comprising CARMA1 (also known as CARD11), BCL10 and MALT1 (the CBM complex). The CBM activates nuclear factor κB (NF-κB) transcription factors by recruiting the 'linear ubiquitin assembly complex' (LUBAC), and unleashes MALT1 paracaspase activity. Although MALT1 enzyme shapes NF-κB signaling, lymphocyte activation and contributes to lymphoma growth, the identity of its substrates continues to be elucidated.