Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA299643 | ENA |
REPOSITORIES: ENA
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Project description:The protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes. MALT1 is not only present in cells of the hematopoietic lineage, but is ubiquitously expressed. Here we report that Zymosan or S. aureus stimulation induced MALT1 protease activity in human primary keratinocytes.
2015-10-24 | GSE74297 | GEO
Project description:The protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes. MALT1 is not only present in cells of the hematopoietic lineage, but is ubiquitously expressed. Here we report that Zymosan or S. aureus stimulation induced MALT1 protease activity in human primary keratinocytes. Human primary keratinocytes were treated for 8 h with solvent control (DMSO), PMA/Ionomycin (P/I) or P/I with MALT1-inhibitor LVSR-fmk. Three biological replicates of each stimualtion were analyzed for gene expression profiles.
2015-10-24 | E-GEOD-74297 | biostudies-arrayexpress
Project description:Constitutive MALT1 activity drives survival of malignant lymphomas addicted to chronic B-cell receptor (BCR) signaling, oncogenic CARD11, or the API2-MALT1 fusion oncoprotein. While MALT1 scaffolding induces NF-kB-dependent survival signaling, MALT1 protease function is thought to augment NF-kB activation by cleaving signaling mediators and transcriptional regulators in B-cell lymphomas. However, the pathological role of MALT1 protease function in lymphomagenesis is not well understood. Here, we show that TRAF6 controls MALT1-dependent activation of NF-kB transcriptional responses, but is dispensable for MALT1 protease activation driven by oncogenic CARD11. To uncouple enzymatic and non-enzymatic functions of MALT1, we analyzed TRAF6-dependent and -independent as well as MALT1 protease-dependent gene expression profiles downstream of oncogenic CARD11 and API2-MALT1. By cleaving and inactivating the RNA binding proteins Regnase-1 and Roquin-1/2, MALT1 protease induces post-transcriptional upregulation of genes like NFKBIZ/IkBz, NFKBID/IkBNS and ZC3H12A/Regnase-1 in activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL). We demonstrate that oncogene-driven MALT1 activity in ABC DLBCL cells regulates NFKBIZ and NFKBID induction on mRNA level via releasing a brake imposed by Regnase-1 and Roquin-1/2. Furthermore, MALT1 protease drives post-transcriptional gene induction in the context of the API2-MALT1 fusion created by the recurrent t(11;18)(q21;q21) translocation in mucosa-associated lymphoid tissue (MALT) lymphoma. Thus, MALT1 paracaspase acts as a bifurcation point for enhancing transcriptional and post-transcriptional gene expression in malignant lymphomas. Moreover, the identification of MALT1 protease selective target genes will provides specific biomarkers for the clinical evaluation of MALT1 inhibitors.
2023-08-25 | GSE215792 | GEO
Project description:We report that the paracaspase Malt1 is required for the development and function of Treg cells. By generating Malt1 conditional knockout and protease dead mutant mice, we found Malt1-loss in Treg cells would lead to early-onset lethal autoimmune disease and the mice would die within 40 days after birth. Interestingly, mice with Treg specific inhibition of Malt1 protease activity develop spontaneous inflammatory disorders.
2018-12-20 | GSE124089 | GEO
Project description:The paracaspase Malt1 is a central regulator of antigen receptor signaling that is frequently mutated in human lymphoma. As a scaffold, it assembles protein complexes for NF-kB activation, and its proteolytic domain cleaves negative NF-kB regulators for signal enforcement. Still, the physiological functions of Malt1-protease are unknown. We demonstrate that targeted Malt1-paracaspase inactivation induces a lethal inflammatory syndrome with lymphocyte-dependent neurodegeneration in vivo. Paracaspase activity is essential for regulatory T-cell and innate-like B-cell development, but it is largely dispensable for overcoming Malt1-dependent thresholds for lymphocyte activation. In addition to NF-kB inhibitors, Malt1 cleaves an entire set of mRNA stability regulators, including Roquin-1, Roquin-2 and Regnase-1, and paracaspase inactivation results in excessive IFNγ production by effector lymphocytes that drives pathology. Together, our results reveal distinct threshold and modulatory functions of Malt1 that differentially control lymphocyte differentiation and activation pathways and demonstrate that selective paracaspase blockage skews systemic immunity towards destructive autoinflammation. Total RNA obtained from T cells with (1h and 4 h) and without stimulation, 3 biological replicates, 3 genotypes (Malt+/-, Malt-/-, MaltPM/-)
2014-10-27 | E-GEOD-55360 | biostudies-arrayexpress
Project description:CARD9 is an adapter protein, which plays a critical role in anti-fungal immunity. However, the role of CARD9 in fungal-induced autophagy remains unknown. In this study, we demonstrated that Card9-/- mice displayed more severe phenotype of zymosan-induced peritonitis, presenting as multiple organs injury and increased systemic inflammation. Moreover, the number of macrophage in spleen was increased in Card9-/- mice. Further studies revealed that autophagy was impaired in peritoneal macrophages of Card9-/- -peritonitis mice. Notably, the autophagy agonist, rapamycin, ameliorated peritonitis in Card9-/- mice. Moreover, Card9 mediates the interaction of Malt1 and P62 upon zymosan stimulation. Together, our results confirmed the protective role of Card9 in the development of peritonitis via regulates autophagy in macrophage cells. The study indicates Card9 may be a potential therapeutic target for peritonitis.
2024-01-01 | GSE164572 | GEO
Project description:The paracaspase Malt1 is a central regulator of antigen receptor signaling that is frequently mutated in human lymphoma. As a scaffold, it assembles protein complexes for NF-kB activation, and its proteolytic domain cleaves negative NF-kB regulators for signal enforcement. Still, the physiological functions of Malt1-protease are unknown. We demonstrate that targeted Malt1-paracaspase inactivation induces a lethal inflammatory syndrome with lymphocyte-dependent neurodegeneration in vivo. Paracaspase activity is essential for regulatory T-cell and innate-like B-cell development, but it is largely dispensable for overcoming Malt1-dependent thresholds for lymphocyte activation. In addition to NF-kB inhibitors, Malt1 cleaves an entire set of mRNA stability regulators, including Roquin-1, Roquin-2 and Regnase-1, and paracaspase inactivation results in excessive IFNγ production by effector lymphocytes that drives pathology. Together, our results reveal distinct threshold and modulatory functions of Malt1 that differentially control lymphocyte differentiation and activation pathways and demonstrate that selective paracaspase blockage skews systemic immunity towards destructive autoinflammation.
2014-10-27 | GSE55360 | GEO
Project description:DA and congenic R11 macrophages were stimulated with zymosan for 1 or 24 hours and pro-inflammatory mediators measured at mRNA level R11 macrophages had reduced pro-inflammatory mediators after stimulation
2010-05-15 | GSE21326 | GEO
Project description:The medicinal active phenothiazine mepazine acts as a small molecule inhibitor of the MALT1 protease. Mepazine selectively inhibits cleavage activity of recombinant and cellular MALT1 by a noncompetitive mechanism. MALT1 activity is required for NF-kappaB signaling and survival of aggressive lymphoma belonging to the ABC-DLBCL (activated B-cell-type of diffuse large B-cell lymphoma) entity. Gene expression profiling was carried out in the ABC-DLBCL cell line HBL1 after treatment with mepazine (20 microM) for 6, 12, and 24 hr. Mepazine inhibits anti-apoptotic NF-kB signaling and thereby survival of these cells. Using Agilent 2-color gene expression microarrays (GPL10332) mepazine-treated HBL1 cells were compared with DMSO in the control channels.
2012-07-31 | E-GEOD-39741 | biostudies-arrayexpress
Project description:The medicinal active phenothiazine mepazine acts as a small molecule inhibitor of the MALT1 protease. Mepazine selectively inhibits cleavage activity of recombinant and cellular MALT1 by a noncompetitive mechanism. MALT1 activity is required for NF-kappaB signaling and survival of aggressive lymphoma belonging to the ABC-DLBCL (activated B-cell-type of diffuse large B-cell lymphoma) entity. Gene expression profiling was carried out in the ABC-DLBCL cell line HBL1 after treatment with mepazine (20 microM) for 6, 12, and 24 hr. Mepazine inhibits anti-apoptotic NF-kB signaling and thereby survival of these cells.
2012-07-31 | GSE39741 | GEO