Article
Immunology
Shan-Yu Fung, Henry Y. Lu, Mehul Sharma, Ashish A. Sharma, Aabida Saferali, Alicia Jia, Libin Abraham, Theo Klein, Michael R. Gold, Luigi D. Noterangelo, Christopher M. Overall, Stuart E. Turvey
Summary: NF-kappa B is a crucial transcription factor regulated by LUBAC, which catalyzes linear ubiquitination of target proteins. Research suggests that MALT1-dependent cleavage impacts HOIL1 modulation of NF-kappa B signaling, affecting the intensity of inflammatory responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Analytical
Shiyi Xie, Cong Zhu, Lijuan Yang, Huiyi Li, Haizhen Zhu, Zhou Nie, Chunyang Lei
Summary: This study presents a ratiometric electrochemical sensor that detects viral proteases with high sensitivity by integrating target proteolysis-activated in vitro transcription and a DNA-functionalized electrochemical interface. The sensor demonstrated robust and specific NS3/4A protease sensing with sub-femtomolar sensitivity, and showed potential for developing direct-acting antivirals and novel therapies for viral infections.
ANALYTICAL CHEMISTRY
(2023)
Article
Environmental Sciences
Dahui Xue, Jinhua Wei, Wencan Lu, Beibei Xia, Shasha Li, Dongmeng Liu, Nan Liu, Xiaomei Wang, Guimiao Lin
Summary: This study investigated the immunotoxicity of BDE-47 and found that it can inhibit the immune response of lymphocytes to LPS by negatively regulating the NF-KB signaling pathway, potentially disrupting immune balance and increasing susceptibility to infectious diseases.
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)
Review
Biochemistry & Molecular Biology
Toshiaki Tanaka, Tomoyuki Nakano, Yasukazu Hozumi, Alberto M. Martelli, Kaoru Goto
Summary: Diacylglycerol kinase (DGK) enzymes phosphorylate diacylglycerol to phosphatidic acid, acting as second messengers to activate cellular responses and regulate stress-responsive transcription factors like p53 and NF-kappa B. Their catalytic and non-catalytic activities modulate gene expression specificity and selectivity.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Oncology
Marthe Minderman, Hildo C. Lantermans, Leonie J. Gruneberg, Saskia A. G. M. Cillessen, Richard J. Bende, Carel J. M. van Noesel, Marie Jose Kersten, Steven T. Pals, Marcel Spaargaren
Summary: The expression level of CYLD is associated with poor prognosis in DLBCL and MCL patients. BCR signaling activates NF-κB by mediating MALT1-induced cleavage of CYLD, leading to its inactivation and degradation. Overexpression of CYLD can suppress NF-κB activity and inhibit the growth of BCR-dependent lymphoma cells.
BLOOD CANCER JOURNAL
(2023)
Article
Virology
Benjamin E. Nilsson-Payant, Skyler Uhl, Adrien Grimont, Ashley S. Doane, Phillip Cohen, Roosheel S. Patel, Christina A. Higgins, Joshua A. Acklin, Yaron Bram, Vasuretha Chandar, Daniel Blanco-Melo, Maryline Panis, Jean K. Lim, Olivier Elemento, Robert E. Schwartz, Brad R. Rosenberg, Rohit Chandwani, Benjamin R. TenOever
Summary: Research suggests that in SARS-CoV-2 infection, NF-kappa B activation plays a crucial role in viral replication in the absence of traditional IFN-I-related transcription factors. Silencing NF-kappa B transcription factors or using inhibitors can reduce virus replication. These findings contribute to a better understanding of SARS-CoV-2 replication mechanisms and provide a basis for the development of novel treatment approaches.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Andrew J. McNamara, Austin D. Brooks, Pranav Danthi
Summary: This study reveals that mammalian reovirus can block the function of NF-κB, an important protein family for the host cell's response to viral infection, through the expression of a viral protein called sigma 3. The expression of sigma 3 diminishes the host's response to infection and promotes viral replication. The differences in NF-κB target gene expression following infection with different reovirus strains are controlled by polymorphisms in the amino acid sequence of sigma 3.
JOURNAL OF VIROLOGY
(2022)
Article
Biology
Nicholas Sim, Yinghui Li
Summary: p52-induced ETS1 overexpression in glioma cells remodels the genome-wide regulatory network of p52 and ETS1 to transcriptionally drive cancer progression. Chronic inflammation promotes glioma progression by activating NF-kappa B signalling, which promotes cancer cell invasion and angiogenesis. Non-canonical NF-kappa B activation directly regulates p52 at the ETS1 promoter, leading to its overexpression and impacting the genomic landscape of ETS1 in a glioma-specific manner.
COMMUNICATIONS BIOLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Haokun Liu, Ying Zhao, Yanfang Wu, Yutong Yan, Xiaoe Zhao, Qiang Wei, Baohua Ma
Summary: Mastitis is a common and important clinical disease in ruminants, which may lead to inflammatory fibrosis if not promptly treated. This study found that Snail plays a critical role in LPS-induced EMT in GMECs, and the mechanism is dependent on the activation of the TLR4/NF-kappa B signaling pathway.
Review
Biochemistry & Molecular Biology
Matthew Martin, Mengyao Sun, Aishat Motolani, Tao Lu
Summary: This article provides an overview of colorectal cancer (CRC) and its stages, types of biomarkers, signaling pathways related to CRC, and the significant role of NF-kappa B in CRC. The authors suggest that more ideal NF-kappa B inhibitors may be developed with the discovery of novel regulators of the pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Qiubo Wang, Yapeng Wang, Qingyang Liu, Ying Chu, Rui Mi, Fengying Jiang, Jingjing Zhao, Kelong Hu, Ran Luo, Yufeng Feng, Harrison Lee, Dong Zhou, Jingyi Mi, Ruoyu Deng
Summary: This study investigates the role of MALT1 in rheumatoid arthritis (RA) and its effect on Th1/2/17 cell differentiation. The results show that MALT1 is increased in RA patients and correlates with disease activity. MALT1 overexpression promotes Th17 differentiation and inhibits Th2 differentiation, while its knockdown has the opposite effect. Furthermore, MALT1's effect on Th2 and Th17 differentiation can be attenuated by NF-kappa B and JNK pathway inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Evolutionary Biology
Michelle M. Leger, Nuria Ros-Rocher, Sebastian R. Najle, Inaki Ruiz-Trillo
Summary: The Rel/NF-kappa B transcription factor family plays diverse roles in immunity, development, and differentiation in animals. New research suggests that these proteins originated earlier than previously thought, in the last common ancestor of animals and fungi. The proteins in the sister group to fungi also contain elements necessary for subcellular regulation of Rel/NF-kappa B, similar to those found in animals.
GENOME BIOLOGY AND EVOLUTION
(2022)
Article
Oncology
Yaomin Li, Xiran Wang, Songtao Qi, Lei Gao, Guanglong Huang, Zhonglu Ren, Kaishu Li, Yuping Peng, Guozhong Yi, Jinglin Guo, Runwei Yang, Hai Wang, Xian Zhang, Yawei Liu
Summary: The study identified that RSRP1 promotes the MES phenotype in GBM by facilitating GBM cell invasion and apoptosis resistance through mediating spliceosome assembly. RSRP1-regulated AS event results in the formation of an oncogenic isoform that is unable to effectively suppress NF-kappa B. Targeting AS via RSRP1-related spliceosomal factors might offer a promising treatment for GBM.
Review
Immunology
Gina Dabbah-Krancher, Andrew L. Snow
Summary: Inborn errors of immunity (IEIs) emphasize the importance of maintaining a balanced immune system to effectively defend against pathogens without causing immunopathology. The nuclear factor of kappa B (NF-kappa B) family of transcription factors play a crucial role in the immune system by regulating genes responsible for lymphocyte function. Recent research on IEIs impacting NF-kappa B activity highlights the need to carefully regulate this pathway to prevent hyperinflammation and immune dysregulation. This article examines specific cases of IEIs caused by mutations in NF-kappa B inducers, regulators, and components, illustrating how these genes maintain an optimal state of NF-kappa B pathway activity for normal adaptive immune system function.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Luping Pang, Manesh Nautiyal, Steff De Graef, Bharat Gadakh, Valentina Zorzini, Anastassios Economou, Sergei Strelkov, Arthur Van Aerschot, Stephen D. Weeks
ACS CHEMICAL BIOLOGY
(2020)
Article
Medicine, Research & Experimental
Jing Cheng, Linda R. Klei, Nathaniel E. Hubel, Ming Zhang, Rebekka Schairer, Lisa M. Maurer, Hanna B. Klei, Heejae Kang, Vincent J. Concel, Phillip C. Delekta, Eric Dang, Michelle A. Mintz, Mathijs Baens, Jason G. Cyster, Narayanan Parameswaran, Margot Thome, Peter C. Lucas, Linda M. McAllister-Lucas
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Hematology
Machteld Sillen, Stephen D. Weeks, Xiaohua Zhou, Andrey A. Komissarov, Galina Florova, Steven Idell, Sergei V. Strelkov, Paul J. Declerck
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2020)
Letter
Biochemistry & Molecular Biology
Elena A. Minina, Jens Staal, Vanina E. Alvarez, John A. Berges, Ilana Berman-Frank, Rudi Beyaert, Kay D. Bidle, Frederic Bornancin, Magali Casanova, Juan J. Cazzulo, Chang Jae Choi, Nuria S. Coll, Vishva M. Dixit, Marko Dolinar, Nicolas Fasel, Christiane Funk, Patrick Gallois, Kris Gevaert, Emilio Gutierrez-Beltran, Stephan Hailfinger, Marina Klemencic, Eugene V. Koonin, Daniel Krappmann, Anna Linusson, Mauricio F. M. Machado, Frank Madeo, Lynn A. Megeney, Panagiotis N. Moschou, Jeremy C. Mottram, Thomas Nystrom, Heinz D. Osiewacz, Christopher M. Overall, Kailash C. Pandey, Juergen Ruland, Guy S. Salvesen, Yigong Shi, Andrei Smertenko, Simon Stael, Jerry Stahlberg, Maria Fernanda Suarez, Margot Thome, Hannele Tuominen, Frank Van Breusegem, Renier A. L. van der Hoorn, Assaf Vardi, Boris Zhivotovsky, Eric Lam, Peter V. Bozhkov
Article
Oncology
Valdemar Priebe, Giulio Sartori, Sara Napoli, Elaine Yee Lin Chung, Luciano Cascione, Ivo Kwee, Alberto Jesus Arribas, Afua Adjeiwaa Mensah, Andrea Rinaldi, Maurilio Ponzoni, Emanuele Zucca, Davide Rossi, Dimitar Efremov, Georg Lenz, Margot Thome, Francesco Bertoni
Article
Immunology
Lerisa Govender, Josip Mikulic, Jean-Christophe Wyss, Olivier Gaide, Margot Thome, Dela Golshayan
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Chemistry, Medicinal
Dries De Ruysscher, Luping Pang, Stijn M. G. Lenders, Davie Cappoen, Paul Cos, Jef Rozenski, Sergei Strelkov, Stephen D. Weeks, Arthur Van Aerschot
Summary: LeuRS is a clinically validated target for antimicrobial development, and bi-substrate inhibitors have shown potent inhibitory activity against bacterial LeuRS. The results of the study could serve as a suitable starting point for further antibiotic development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Luping Pang, Stephen D. Weeks, Arthur Van Aerschot
Summary: Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in all three kingdoms of life, and have been recognized as suitable targets for small molecule anti-infectives. This review discusses the catalytic activities of aaRSs, inhibitory mechanisms, and species-selectivity determinants of reported inhibitors. The structural perspective highlights opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Madeline Loffredo, Hector Lucero, Da-Yuan Chen, Aoife O'Connell, Simon Bergqvist, Ahmad Munawar, Asanga Bandara, Steff De Graef, Stephen D. Weeks, Florian Douam, Mohsan Saeed, Ali H. Munawar
Summary: Multiple studies have suggested the repositioning of famotidine, an approved drug, for the treatment of COVID-19 due to the lack of specific antiviral drugs for the coronavirus. While potential molecular targets have been proposed, experimental results show that famotidine does not directly inhibit SARS-CoV-2 replication. Further research is needed to explore the molecular mechanism of famotidine in the context of COVID-19.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Luping Pang, Stephen D. Weeks, Martin Juhas, Sergei Strelkov, Jan Zitko, Arthur Van Aerschot
Summary: HcProRS catalyzes prolyl-tRNA synthesis and inhibiting its activity may benefit treatment of fibrosis, autoimmune diseases, and cancer. Recent research identified potential novel HcProRS inhibitors from a pyrazinamide-based compound library, showing promise for repurposing old drug candidates for HcProRS-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Giulio Sartori, Sara Napoli, Luciano Cascione, Elaine Yee Lin Chung, Valdemar Priebe, Alberto Jesus Arribas, Afua Adjeiwaa Mensah, Michela Dall'Angelo, Chiara Falzarano, Laura Barnabei, Mattia Forcato, Andrea Rinaldi, Silvio Bicciato, Margot Thome, Francesco Bertoni
Summary: FLI1 is more highly expressed in GCB DLBCL compared to ABC DLBCL and regulates a network of biologically crucial genes. It directly influences the NF-kappa B pathway at the transcriptional level and the alternative NF-kappa B pathway via ASB2, providing a potential new therapeutic approach for GCB DLBCL.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biology
Luping Pang, Vladimir Zanki, Sergei Strelkov, Arthur Van Aerschot, Ita Gruic-Sovulj, Stephen D. Weeks
Summary: Crystal structures of leucyl-tRNA synthetase in Neisseria gonorrhoeae reveal conformational changes and a peptide-plane flip in the active site that correlate with catalytic steps. These structural alterations have a significant impact on the enzyme's activity.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Luping Pang, Stijn Lenders, Evgenii M. Osipov, Stephen D. Weeks, Jef Rozenski, Tatiana Piller, Davie Cappoen, Sergei V. Strelkov, Arthur Van Aerschot
Summary: Mycothiol (MSH) is the major cellular thiol in Mycobacterium tuberculosis (Mtb) and plays a crucial role in the resistance to antibiotics and oxidative stresses. This study focused on MshC, an enzyme involved in the synthesis of MSH, and synthesized five new compounds with potential inhibitory effects on MshC. The compounds showed strong binding affinity with MshC, but did not suppress the growth of Mtb culture, possibly due to inadequate cellular uptake.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Evgenii M. Osipov, Ali H. Munawar, Steven Beelen, Daren Fearon, Alice Douangamath, Conor Wild, Stephen D. Weeks, Arthur Van Aerschot, Frank von Delft, Sergei Strelkov
Summary: Polyomaviruses, including BK polyomavirus and Merkel cell polyomavirus, are human pathogens for which no specific drugs are available. In this study, we focused on the structural protein VP1 of BK polyomavirus and used high-throughput screening to identify drug-like fragments that bind to truncated VP1 pentamers. We found a total of 144 binding hits, which cluster in six surface pockets. These findings provide a foundation for rational drug design targeting polyomavirus capsid assembly.
RSC CHEMICAL BIOLOGY
(2022)
Meeting Abstract
Medicine, General & Internal
Lerisa Govender, Josip Mikulic, Jean-Christophe Wyss, Olivier Gaide, Margot Thome, Dela Golshayan
SWISS MEDICAL WEEKLY
(2020)