دورية أكاديمية
MALT1 substrate cleavage: what is it good for?
| العنوان: | MALT1 substrate cleavage: what is it good for? |
|---|---|
| المؤلفون: | Moud BN; Research Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany., Ober F; Research Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany., O'Neill TJ; Research Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany., Krappmann D; Research Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. |
| المصدر: | Frontiers in immunology [Front Immunol] 2024 May 28; Vol. 15, pp. 1412347. Date of Electronic Publication: 2024 May 28 (Print Publication: 2024). |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein*/metabolism , Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein*/genetics , Signal Transduction*, Humans ; Animals ; Substrate Specificity ; B-Cell CLL-Lymphoma 10 Protein/metabolism ; B-Cell CLL-Lymphoma 10 Protein/genetics ; CARD Signaling Adaptor Proteins/metabolism ; CARD Signaling Adaptor Proteins/genetics ; Proteolysis ; TNF Receptor-Associated Factor 6/metabolism |
| مستخلص: | CARD-BCL10-MALT1 (CBM) signalosomes connect distal signaling of innate and adaptive immune receptors to proximal signaling pathways and immune activation. Four CARD scaffold proteins (CARD9, 10, 11, 14) can form seeds that nucleate the assembly of BCL10-MALT1 filaments in a cell- and stimulus-specific manner. MALT1 (also known as PCASP1) serves a dual function within the assembled CBM complexes. By recruiting TRAF6, MALT1 acts as a molecular scaffold that initiates IκB kinase (IKK)/NF-κB and c-Jun N-terminal kinase (JNK)/AP-1 signaling. In parallel, proximity-induced dimerization of the paracaspase domain activates the MALT1 protease which exerts its function by cleaving a set of specific substrates. While complete MALT1 ablation leads to immune deficiency, selective destruction of either scaffolding or protease function provokes autoimmune inflammation. Thus, balanced MALT1-TRAF6 recruitment and MALT1 substrate cleavage are critical to maintain immune homeostasis and to promote optimal immune activation. Further, MALT1 protease activity drives the survival of aggressive lymphomas and other non-hematologic solid cancers. However, little is known about the relevance of the cleavage of individual substrates for the pathophysiological functions of MALT1. Unbiased serendipity, screening and computational predictions have identified and validated ~20 substrates, indicating that MALT1 targets a quite distinct set of proteins. Known substrates are involved in CBM auto-regulation (MALT1, BCL10 and CARD10), regulation of signaling and adhesion (A20, CYLD, HOIL-1 and Tensin-3), or transcription (RelB) and mRNA stability/translation (Regnase-1, Roquin-1/2 and N4BP1), indicating that MALT1 often targets multiple proteins involved in similar cellular processes. Here, we will summarize what is known about the fate and functions of individual MALT1 substrates and how their cleavage contributes to the biological functions of the MALT1 protease. We will outline what is needed to better connect critical pathophysiological roles of the MALT1 protease with the cleavage of distinct substrates. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Moud, Ober, O’Neill and Krappmann.) |
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| فهرسة مساهمة: | Keywords: API2-MALT1; CBM complex; MALT1; RNA metabolism; auto-regulation; cell signaling; protease; substrate cleavage |
| المشرفين على المادة: | EC 3.4.22.- (Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein) EC 3.4.22.- (MALT1 protein, human) 0 (B-Cell CLL-Lymphoma 10 Protein) 0 (CARD Signaling Adaptor Proteins) 0 (TNF Receptor-Associated Factor 6) |
| تواريخ الأحداث: | Date Created: 20240612 Date Completed: 20240612 Latest Revision: 20240613 |
| رمز التحديث: | 20240614 |
| مُعرف محوري في PubMed: | PMC11165066 |
| DOI: | 10.3389/fimmu.2024.1412347 |
| PMID: | 38863711 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2024.1412347 |