Article
Immunology
Thomas J. O'Neill, Andreas Gewies, Thomas Seeholzer, Daniel Krappmann
Summary: MALT1 is a core component of the CBM signalosome, acting as a scaffold and protease. It connects TCR ligation to immune activation and controls the development of Treg cells. TRAF6 ablation leads to activation of Tconv cells, while MALT1 protease inactivation prevents autoinflammation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Vijay Kondreddy, Shiva Keshava, Kaushik Das, Jhansi Magisetty, L. Vijaya Mohan Rao, Usha R. Pendurthi
Summary: This study reveals the important role of the Gab2-MALT1 axis in thromboinflammation. Targeting this axis may be an effective strategy to treat DVT without inducing bleeding complications.
Article
Biochemistry & Molecular Biology
Beatriz Gomez Solsona, Anja Schmitt, Klaus Schulze-Osthoff, Stephan Hailfinger
Summary: The paracaspase MALT1 plays a crucial role in immune system and its deregulated activity is associated with cancer. Pharmacological targeting of MALT1 may represent a promising anti-cancer strategy.
Review
Biochemistry & Molecular Biology
Thomas D. Gilmore
Summary: NF-kappa B is extensively studied for its roles in cancer development and is often constitutively or aberrantly activated in human cancers. Activation can occur due to mutations in NF-kappa B factors, upstream regulators, or pathways impacting NF-kappa B. Despite being considered an anticancer strategy, inhibition of NF-kappa B has had limited success in cancer treatment.
Review
Biochemistry & Molecular Biology
Stephan Hailfinger, Klaus Schulze-Osthoff
Summary: Psoriasis is a common autoimmune-related skin disease that involves various cell types. Mutations in genes such as CARD14 can contribute to the development of the disease. The activation of MALT1, a key signaling molecule, plays a significant role in psoriasis by activating transcription factors and mediating disease progression through its protease activity and molecular scaffold function.
BIOLOGICAL CHEMISTRY
(2021)
Article
Immunology
Thomas J. O'Neill, Thomas Seeholzer, Andreas Gewies, Torben Gehring, Florian Giesert, Isabel Hamp, Carina Grass, Henrik Schmidt, Katharina Kriegsmann, Marie J. Tofaute, Katrin Demski, Tanja Poth, Marc Rosenbaum, Theresa Schnalzger, Juergen Ruland, Martin Goettlicher, Mark Kriegsmann, Ronald Naumann, Vigo Heissmeyer, Oliver Plettenburg, Wolfgang Wurst, Daniel Krappmann
Summary: TRAF6 functions as a signaling accelerator for MALT1 scaffolding in activated T cells and as a molecular brake for MALT1 protease in resting T cells. Disruption of TRAF6-mediated homeostatic suppression of MALT1 protease leads to severe autoimmune inflammation, which can be completely reverted by genetic or therapeutic inactivation of MALT1 protease function.
SCIENCE IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ioannis Skordos, Yasmine Driege, Mira Haegman, Marja Kreike, Jens Staal, Annelies Demeyer, Rudi Beyaert
Summary: The unique activity of MALT1 protease in controlling immunity in humans has made it an attractive target for autoimmune diseases and lymphoid malignancies. This study investigates the role of MALT1-mediated cleavage of HOIL-1 in T and B cell development and function using knock-in mice, and shows that it has no significant impact on these processes.
Review
Immunology
Henry Y. Lu, Stuart E. Turvey
Summary: Human germline MALT1 deficiency is an inborn error of immunity characterized by recurrent infections and failure to thrive. The number of identified patients has significantly increased in the past two years, leading to a better understanding of the clinical features of this disorder. Patients commonly experience respiratory, skin, gastrointestinal, and blood system infections.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Stefan Schiesser, Peter Hajek, Huw E. Pople, Helena Kack, Linda Oster, Rhona J. Cox
Summary: The discovery and optimization of a novel series of allosteric MALT1 inhibitors, resulting in compound 8 with high cell potency, signifies a promising strategy to modulate NF-kB signaling for potential treatment of B-cell lymphoma and autoimmune diseases. X-ray analysis confirmed compound 8 binds to an induced allosteric site in MALT1, and its excellent in vivo rat PK profile makes it a promising lead for further optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ken Nunettsu Asaba, Yohei Adachi, Kazuyuki Tokumaru, Akira Watanabe, Yasufumi Goto, Takumi Aoki
Summary: The novel series of 1,5-bisphenylpyrazoles discovered in this study showed potent inhibition against MALT1, with compound 33 demonstrating strong activity, cellular potency, and high selectivity against other caspases. Kinetic study results indicated that compound 33 is a non-competitive inhibitor of MALT1 protein.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Plant Sciences
Eshan Sharma, Akanksha Bhatnagar, Avantika Bhaskar, Susmita M. Majee, Martin Kieffer, Stefan Kepinski, Paramjit Khurana, Jitendra P. Khurana
Summary: The rice FB protein-coding gene OsFBX257 is differentially expressed under drought conditions and other abiotic stresses. It plays a significant role in modulating root architecture and improving drought stress tolerance in rice. OsFBX257 is a potential breeding target for alleviating drought stress-induced damage in rice.
PLANT CELL AND ENVIRONMENT
(2023)
Article
Chemistry, Medicinal
Paul Gehrtz, Shir Marom, Mike Buehrmann, Julia Hardick, Silke Kleinboelting, Amit Shraga, Christian Dubiella, Ronen Gabizon, Jan N. Wiese, Matthias P. Mueller, Galit Cohen, Ilana Babaev, Khriesto Shurrush, Liat Avram, Efrat Resnick, Haim Barr, Daniel Rauh, Nir London
Summary: High-throughput nanomole-scale synthesis allows for efficient and economical late-stage functionalization of compounds. Copper-catalyzed azide-alkyne cycloaddition has been demonstrated to be capable of nanoscale late-stage functionalization of covalent kinase inhibitors, enabling the synthesis of hundreds of compounds that do not require purification for biological assay screening. This study presents a promising approach to improving the properties of lead chemical matter through high-throughput late-stage functionalization of covalent inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biology
Yang Chen, Pengfei Wang, Qi Li, Xiaolong Yan, Tianjun Xu
Summary: This study identifies calpain2a as a key regulator of antibacterial and antiviral immunity in teleost fish. It interacts with TRAF6, promoting TRAF6 degradation and inhibiting TRAF6 dimerization and auto-ubiquitination.
COMMUNICATIONS BIOLOGY
(2023)
Review
Chemistry, Medicinal
Xuewu Liang, YiChun Cao, Chunpu Li, Haolan Yu, Chenghua Yang, Hong Liu
Summary: MALT1 is a key adaptor protein involved in regulating the NF-κB pathway, and its abnormal expression is associated with various diseases. Pharmacological regulation of MALT1 may hold promise for the treatment of lymphoma and related conditions. Current research is focused on the development of MALT1 inhibitors and exploring their therapeutic potential.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Immunology
Zsuzsanna Kurgyis, Larsen Vornholz, Konstanze Pechloff, Lajos V. Kemeny, Tim Wartewig, Andreas Muschaweckh, Abhinav Joshi, Katja Kranen, Lara Hartjes, Sigrid Moeckel, Katja Steiger, Erik Hameister, Thomas Volz, Mark Mellett, Lars E. French, Tilo Biedermann, Thomas Korn, Juergen Ruland
Summary: The BCL10/MALT1 signalosome plays a crucial role in psoriatic skin inflammation by acting as both initiators and amplifiers of the pathology. Its aberrant activity is frequently detected in the skin of human sporadic psoriasis, indicating a potential therapeutic target for the treatment of psoriasis.
SCIENCE IMMUNOLOGY
(2021)
Article
Gastroenterology & Hepatology
Xiaoting Sun, Xingkang He, Yin Zhang, Kayoko Hosaka, Patrik Andersson, Jing Wu, Jieyu Wu, Xu Jing, Qiqiao Du, Xiaoli Hui, Bo Ding, Ziheng Guo, An Hong, Xuan Liu, Yan Wang, Qing Ji, Rudi Beyaert, Yunlong Yang, Qi Li, Yihai Cao
Summary: The study found that IL-33 and CXCL3 are elevated in PDAC patients, correlated with tumor inflammation and poor survival rates. The IL-33-ST2-MYC pathway regulates the high production of CXCL3. Activation of CXCR2 by CXCL3 induces a CAF-to-myoCAF transition, promoting PDAC metastasis.
Editorial Material
Plant Sciences
Jianbin Su, Yi-Ju Lu, Jens Staal, Agnieszka Ludwikow
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Domien Vanneste, Jens Staal, Mira Haegman, Yasmine Driege, Marieke Carels, Elien Van Nuffel, Pieter De Bleser, Yvan Saeys, Rudi Beyaert, Inna S. Afonina
Summary: Prostate cancer is one of the most common cancer types in men, and its increasing prevalence worldwide is attributed to the influence of modern Western lifestyle. Through analysis of cancer databases, it has been found that overexpression of CARD14 is strongly associated with aggressive prostate cancer in human patients. Furthermore, it has been demonstrated that CARD14-induced signaling plays a role in regulating prostate cancer cell survival and gene expression.
Article
Oncology
Olga S. Blomberg, Lorenzo Spagnuolo, Hannah Garner, Leonie Voorwerk, Olga I. Isaeva, Ewald van Dyk, Noor Bakker, Myriam Chalabi, Chris Klaver, Maxime Duijst, Kelly Kersten, Marieke Bruggemann, Dorien Pastoors, Cheei-Sing Hau, Kim Vrijland, Elisabeth A. M. Raeven, Daphne Kaldenbach, Kevin Kos, Inna S. Afonina, Paulien Kaptein, Louisa Hoes, Willemijn S. M. E. Theelen, Paul Baas, Emile E. Voest, Rudi Beyaert, Daniela S. Thommen, Lodewyk F. A. Wessels, Karin E. de Visser, Marleen Kok
Summary: Immune checkpoint blockade (ICB) has revolutionized cancer therapy by promoting effective immune responses through the activation of CD4(+) T cells and the recruitment of eosinophils. This study demonstrates the critical role of eosinophils in ICB response and provides proof-of-principle for enhancing ICB efficacy through eosinophil engagement. Mechanistically, ICB increases IL-5 production, stimulating elevated eosinophil production and systemic eosinophil expansion.
Article
Biochemistry & Molecular Biology
Ioannis Skordos, Yasmine Driege, Mira Haegman, Marja Kreike, Jens Staal, Annelies Demeyer, Rudi Beyaert
Summary: The unique activity of MALT1 protease in controlling immunity in humans has made it an attractive target for autoimmune diseases and lymphoid malignancies. This study investigates the role of MALT1-mediated cleavage of HOIL-1 in T and B cell development and function using knock-in mice, and shows that it has no significant impact on these processes.
Article
Immunology
Leslie Naesens, Santoshi Muppala, Dhiraj Acharya, Josephine Nemegeer, Delfien Bogaert, Jung-Hyun Lee, Katrien Staes, Veronique Debacker, Marieke De Bruyne, Pieter De Bleser, Elfride De Baere, Michiel van Gent, GuanQun Liu, Bart N. Lambrecht, Jens Staal, Tessa Kerre, Rudi Beyaert, Jonathan Maelfait, Simon J. Tavernier, Michaela U. Gack, Filomeen Haerynck
Summary: This study identified compound heterozygous loss-of-function mutations in the gene GTF3A, which encodes for transcription factor IIIA (TFIIIA), leading to impaired innate immune responses against herpes simplex virus 1 (HSV-1) and increased viral replication. It was found that TFIIIA plays a crucial role in the activation of the RNA sensor RIG-I. These findings highlight the association between GTF3A genetic defects and susceptibility to HSV-1-induced encephalitis.
SCIENCE IMMUNOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Femke De Meyer, Inna S. Afonina
Summary: Linear ubiquitination, an important post-translational modification, plays a regulatory role in the activation of proinflammatory signalling mediators. Aberrant linear ubiquitination is implicated in the development of inflammatory and autoimmune diseases. This study reveals a new role for linear ubiquitination in stabilizing the NFAT1 transcription factor, resulting in enhanced NFAT1-mediated gene expression, potentially impacting patients with Kawasaki disease.
Article
Allergy
Aurora Holgado, Zhuangzhuang Liu, Aigerim Aidarova, Christina Mueller, Mira Haegman, Yasmine Driege, Marja Kreike, Charlotte L. Scott, Inna S. Afonina, Rudi Beyaert
Summary: IL-33 plays a crucial role in allergic diseases, and A20 is involved in regulating IL-33 signaling. In the absence of A20 in macrophages, IL-33-induced lung immune responses are altered, with reduced type 2 immune response and increased production of IFN-gamma. This study reveals a novel role for A20 in regulating IL-33-induced STAT1 signaling in macrophages.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Domien Vanneste, Qiang Bai, Shakir Hasan, Wen Peng, Dimitri Pirottin, Joey Schyns, Pauline Marechal, Cecilia Ruscitti, Margot Meunier, Zhaoyuan Liu, Celine Legrand, Laurence Fievez, Florent Ginhoux, Coraline Radermecker, Fabrice Bureau, Thomas Marichal
Summary: Using a mouse model, researchers found that engrafted Ly6C(+) classical monocytes proliferate locally in a Csf1 receptor-dependent manner before differentiating into lung interstitial macrophages.
Article
Immunology
Tineke Vanderhaeghen, Steven Timmermans, Melanie Eggermont, Deepika Watts, Jolien Vandewalle, Charlotte Wallaeys, Louise Nuyttens, Joyca De Temmerman, Tino Hochepied, Sylviane Dewaele, Joke Vanden Berghe, Niek Sanders, Ben Wielockx, Rudi Beyaert, Claude Libert
Summary: Polymicrobial sepsis leads to anorexia, resulting in lipolysis in white adipose tissue and proteolysis in muscle, leading to the release of FFAs, glycerol, and gluconeogenic amino acids. Dysfunction of PPAR alpha and GR in the liver causes the accumulation of metabolites and the failure to produce ketone bodies and glucose, leading to toxicity. Hypoxia and activation of HIFs were investigated as potential causes for this dysfunction, but the results suggest that HIF1 alpha and HIF2 alpha are activated in hepatocytes in sepsis, but their contribution to lethality is minimal.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alessio Borio, Aurora Holgado, Christina Passegger, Herbert Strobl, Rudi Beyaert, Holger Heine, Alla Zamyatina
Summary: The TLR4/MD-2 complex is a crucial receptor in the innate immune system and plays a major role in inflammation, but dysregulation in its signaling can lead to uncontrolled inflammation and disease. Targeting this receptor complex with anti-inflammatory therapies is promising, but the complexity of ligand recognition and species-specificity presents challenges. Researchers have developed glycolipids that mimic lipid A and inhibit TLR4-mediated inflammation, and these glycolipids were evaluated for their activity in human and murine immune cells. A bis-phosphorylated glycolipid was found to have antagonist activity on human TLR4, but acted as a partial agonist on murine TLR4.
Editorial Material
Immunology
Jens Staal, Luz Pamela Blanco, Andras Perl
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Leonie Wittner, Lukas Wagener, Jakob J. Wiese, Iris Stolzer, Susanne M. Krug, Elisabeth Naschberger, Rene Jackstadt, Rudi Beyaert, Raja Atreya, Anja A. Kuehl, Gregor Sturm, Miguel Gonzalez-Acera, Jay V. Patankar, Christoph Becker, Britta Siegmund, Zlatko Trajanoski, Beate Winner, Markus F. Neurath, Michael Schumann, Claudia Guenther
Summary: The paracaspase MALT1 plays a crucial role in mucosal inflammation. It is highly expressed in colonic epithelial cells of UC patients and experimental colitis. Mechanistically, MALT1 protease function inhibits ferroptosis and contributes to NF-kappa B signaling and STAT3 signaling, which are involved in inflammation and tissue healing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)