{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T03:35:24Z","timestamp":1793936124502,"version":"4.8.0"},"reference-count":60,"publisher":"American Society of Hematology","issue":"23","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Constitutive mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) activity drives survival of malignant lymphomas addicted to chronic B-cell receptor signaling, oncogenic CARD11, or the API2-MALT1 (also BIRC3::MALT1) fusion oncoprotein. Although MALT1 scaffolding induces NF-\u03baB\u2013dependent survival signaling, MALT1 protease function is thought to augment NF-\u03baB 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-\u03baB transcriptional responses but is dispensable for MALT1 protease activation driven by oncogenic CARD11. To uncouple enzymatic and nonenzymatic functions of MALT1, we analyzed TRAF6-dependent and -independent as well as MALT1 protease\u2013dependent gene expression profiles downstream of oncogenic CARD11 and API2-MALT1. The data suggest that by cleaving and inactivating the RNA binding proteins Regnase-1 and Roquin-1\/2, MALT1 protease induces posttranscriptional upregulation of many genes including NFKBIZ\/I\u03baB\u03b6, NFKBID\/I\u03baBNS, and ZC3H12A\/Regnase-1 in activated B-cell\u2013like diffuse large B-cell lymphoma (ABC DLBCL). We demonstrate that oncogene-driven MALT1 activity in ABC DLBCL cells regulates NFKBIZ and NFKBID induction on an mRNA level via releasing a brake imposed by Regnase-1 and Roquin-1\/2. Furthermore, MALT1 protease drives posttranscriptional gene induction in the context of the API2-MALT1 fusion created by the recurrent t(11;18)(q21;q21) translocation in MALT lymphoma. Thus, MALT1 paracaspase acts as a bifurcation point for enhancing transcriptional and posttranscriptional gene expression in malignant lymphomas. Moreover, the identification of MALT1 protease\u2013selective target genes provides specific biomarkers for the clinical evaluation of MALT1 inhibitors.<\/jats:p>","DOI":"10.1182\/blood.2023021299","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T13:04:23Z","timestamp":1692968663000},"page":"1985-2001","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["Oncogene-induced MALT1 protease activity drives posttranscriptional gene expression in malignant lymphomas"],"prefix":"10.1182","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9799-8983","authenticated-orcid":false,"given":"Nicole","family":"Wimberger","sequence":"first","affiliation":[{"name":"1Research Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets Therapeutic Center, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Ober","sequence":"additional","affiliation":[{"name":"1Research Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets Therapeutic Center, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-1154","authenticated-orcid":false,"given":"G\u00f6ksu","family":"Avar","sequence":"additional","affiliation":[{"name":"2Department of Computational Health, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"},{"name":"3Department of Biology, Ludwig Maximilian University Munich, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1909-0133","authenticated-orcid":false,"given":"Michael","family":"Grau","sequence":"additional","affiliation":[{"name":"4Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendan","family":"Xu","sequence":"additional","affiliation":[{"name":"4Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4728-1693","authenticated-orcid":false,"given":"Georg","family":"Lenz","sequence":"additional","affiliation":[{"name":"4Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0267-5792","authenticated-orcid":false,"given":"Michael P.","family":"Menden","sequence":"additional","affiliation":[{"name":"2Department of Computational Health, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"},{"name":"3Department of Biology, Ludwig Maximilian University Munich, Martinsried, Germany"},{"name":"5Department of Biochemistry and Pharmacology, The University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7640-3234","authenticated-orcid":false,"given":"Daniel","family":"Krappmann","sequence":"additional","affiliation":[{"name":"1Research Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets Therapeutic Center, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, 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