Post-translational modification of MALT1 and its role in B cell- and T cell-related diseases

Zhang, Yiyue; Peng, Jun; Luo, Xiu-Ju

doi:10.1016/j.bcp.2022.114977

Cited by 8 publications

(6 citation statements)

References 162 publications

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“…Molecular docking further revealed that the main binding forces between MALT1 and telaprevir were side chain binding and backbone binding (Figure D). Furthermore, the most abundant GO terms and KEGG pathway displayed that the potential targets of telaprevir were closely associated with immune, necroptosis, apoptosis, calcium signaling pathways, and neurodegenerative diseases, which was consistent with the function of MALT1 recently reported in mice suffering ischemic/reperfusion, , suggesting that the phenotypic effects of telaprevir were intimately related to the role of MALT1 in ischemic stroke (Figure E,F).…”

Section: Resultssupporting

confidence: 86%

“…In agreement with our recent report, 9 upregulation of MALT1 was observed in the brain of stroke mice, accompanied by the increased levels of necroptosisrelevant proteins (receptor-interacting serine/threonine-protein kinase 1 [RIPK1]/p-RIPK1, receptor-interacting serine/ threonine-protein kinase 3 [RIPK3]/p-RIPK3, and mixed lineage kinase domain-like protein [MLKL]/p-MLKL); these phenomena were reversed by telaprevir, except RIPK3 (Figure 7A−H). These results suggest that telaprevir suppresses the RIPK1/RIPK3/MLKL pathway via targeting MALT1.…”

Section: Telaprevir Reduced Necroptosis In the Brain Of Stroke Micesupporting

confidence: 94%

“…Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an inflammatory regulatory molecule that has been reported to play an important role in a variety of autoimmune diseases and tumors . Interestingly, our recent studies have demonstrated that MALT1 exerted an essential role in ischemic stroke, mainly involving GluN2B activation, Ca 2+ overload, excitotoxicity, and necroptosis. , Therefore, MALT1 might be a novel drug target for the therapy of ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

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Telaprevir Improves Memory and Cognition in Mice Suffering Ischemic Stroke via Targeting MALT1-Mediated Calcium Overload and Necroptosis

Zhang

Peng

Chen

et al. 2023

ACS Chem. Neurosci.

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Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has been confirmed to contribute to brain injury in ischemic stroke via promoting excitotoxicity and necroptosis. Telaprevir, a hepatitis C virus protease inhibitor, is predicted to be a potential MALT1 inhibitor. Here, we showed that telaprevir protected against cerebral ischemic injury via inhibiting MALT1, thereby preventing glutamate receptor ionotropic NMDA 2B (GluN2B) activation, limiting calcium overload, and suppressing necroptosis. In ischemic stroke mice, telaprevir reduced infarct volume, improved the long-term survival rate, and enhanced sensorimotor, memory, and cognitive functions. In hypoxia-treated nerve cells, telaprevir decreased the intracellular calcium concentrations and reduced LDH release. Mechanistically, telaprevir inhibited MALT1 protease activity, thus decreasing the membrane protein level of GluN2B and its phosphorylation through reducing the level of STEP61. Moreover, telaprevir was able to inhibit the levels of necroptosis-associated proteins. According to these results, it can be concluded that telaprevir alleviates neuronal brain injury in stroke mice via restraining GluN2B activation and suppresses the receptor-interacting protein kinase 1 (RIPK1)/ receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudokinase (MLKL) pathway through inhibiting MALT1. Thus, telaprevir might have a novel indication for treating patients with ischemic stroke.

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Section: Resultssupporting

confidence: 86%

Section: Telaprevir Reduced Necroptosis In the Brain Of Stroke Micesupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Telaprevir Improves Memory and Cognition in Mice Suffering Ischemic Stroke via Targeting MALT1-Mediated Calcium Overload and Necroptosis

Zhang

Peng

Chen

et al. 2023

ACS Chem. Neurosci.

Self Cite

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“…Similarly, the adaptive immune response allows recognition of non-self-antigens and the synthesis of antibodies because of cell or body fluid. Cell-mediated immunity consists of T lymphocytes that recognize antigens treated by antigen-presenting cells through their T cell receptors (TCR) [30,31]. These cells participate in innate immune responses that require NF-κB activation.…”

Section: Discussionmentioning

confidence: 99%

Tetrahydrocurcumin regulates the tumor immune microenvironment to inhibit breast cancer proliferation and metastasis via the CYP1A1/NF-κB signaling pathway

Zeng

Bao

et al. 2023

Cancer Cell Int

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The NF-κB signaling pathway is overactivated in tumor cells, and the activation of the NF-κB signaling pathway releases a large number of inflammatory factors, which enhance tumor immunosuppression and promote tumor metastasis. The cytochrome P450 (CYP450) system consists of important metabolic enzymes present in different tissues and progressive tumors, which may lead to changes in the pharmacological action of drugs in inflammatory diseases such as tumors. In this study, the anticancer effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on breast cancer cells and the underlying mechanism were investigated. Result showed that THC selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner. Moreover, THC-induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species (ROS) induction. In addition, THC could affect the CYP450 enzyme metabolic pathway and inhibit the expression of CYP1A1 and activation of the NF-κB pathway, thereby inhibiting the migration and invasion of breast cancer cells. Furthermore, after overexpression of CYP1A1, the inhibitory effects of THC on the proliferation, metastasis, and induction of apoptosis in breast cancer cells were weakened. The knockdown of CYP1A1 significantly enhanced the inhibitory effect of THC on the proliferation, metastasis, and apoptosis induction of breast cancer cells. Notably, THC exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MCF-7 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Collectively, these results showed that TH could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the CYP1A1/NF-κB signaling pathway, indicating that THC serves as a potential candidate drug for the treatment of breast cancer.

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“…By bridging T or B cell antigen receptor (TCR/BCR) signaling pathways, the MALT1-mediated NF-κB pathway participates in multiple immunological and proinflammatory processes and its genetic abnormalities may lead to a range of diseases, including various types of lymphomas, solid tumors, and autoimmune diseases. − Upregulation of MALT1 activity is observed in many activated B cell type lymphomas, often due to function-enhancing mutations in MALT1 upstream proteins, thereby deregulating NF-κB-driven lymphocyte proliferation . The constitutive activation of MALT1 is a common feature in a number of B cell malignancies, among which MALT lymphoma and DLBCL are well-understood (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Development of Potent MALT1 Inhibitors Featuring a Novel “2-Thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-one” Scaffold for the Treatment of B Cell Lymphoma

Liang,

Yu,

Liang

et al. 2024

J. Med. Chem.

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Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has emerged as a novel and promising therapeutic target for the treatment of lymphomas and autoimmune diseases. Herein, we reported a new class of MALT1 inhibitors featuring a novel "2-thioxo-2,3-dihydrothiazolo[4,5d]pyrimidin-7(6H)-one" scaffold developed by structure-based drug design. Structure−activity relationship studies finally led to the discovery of MALT1 inhibitor 10m, which covalently and potently inhibited MALT1 protease with the IC 50 value of 1.7 μM. 10m demonstrated potent and selective antiproliferative activity against ABC-DLBCL and powerful ability to induce HBL1 apoptosis. 10m also effectively downregulated the activities of MALT1 and its downstream signal pathways. Furthermore, 10m induced upregulation of mTOR and PI3K-Akt signals and exhibited a synergistic antitumor effect with Rapamycin in HBL1 cells. More importantly, 10m remarkably suppressed the tumor growth both in the implanted HBL1 and TMD8 xenograft models. Collectively, this work provides valuable MALT1 inhibitors with a distinct core structure.

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Post-translational modification of MALT1 and its role in B cell- and T cell-related diseases

Cited by 8 publications

References 162 publications

Telaprevir Improves Memory and Cognition in Mice Suffering Ischemic Stroke via Targeting MALT1-Mediated Calcium Overload and Necroptosis

Telaprevir Improves Memory and Cognition in Mice Suffering Ischemic Stroke via Targeting MALT1-Mediated Calcium Overload and Necroptosis

Tetrahydrocurcumin regulates the tumor immune microenvironment to inhibit breast cancer proliferation and metastasis via the CYP1A1/NF-κB signaling pathway

Development of Potent MALT1 Inhibitors Featuring a Novel “2-Thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-one” Scaffold for the Treatment of B Cell Lymphoma

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