Article
Cell Biology
Wenjie Zuo, Mai Wakimoto, Noriyasu Kozaiwa, Yutaro Shirasaka, Seong-Wook Oh, Shiori Fujiwara, Hitoshi Miyachi, Amane Kogure, Hiroki Kato, Takashi Fujita
Summary: RIG-I-like receptors, protein kinase R, and endosomal Toll-like receptor 3 are important in sensing viral RNA and determining cell fate. Short 5'-triphosphate dsRNA induces slow apoptosis dependent on IRF-3 and IFN-I, while intracellular long dsRNA is sensed by PKR and TLR3, which activate distinct signals and synergistically induce rapid apoptosis.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Rouven Schulz, Medina Korkut-Demirbas, Gloria Colombo, Sandra Siegert
Summary: This study introduces a chemogenetic approach to study G protein-coupled receptors (GPCRs) by designing GPCR chimeras that can mimic the functions of the target receptors without knowing their immediate ligands. The researchers demonstrate the successful use of this approach in studying the beta 2-adrenergic receptor in microglia and its role in inflammation. The results show that the chimeric receptors exhibit similar responses to the endogenous receptors in terms of signaling pathways and cellular processes. This new approach allows for the investigation of cell type-specific pathways without the need for known ligands.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Marten A. Hoeksema, Zeyang Shen, Inge R. Holtman, An Zheng, Nathan J. Spann, Isidoro Cobo, Melissa Gymrek, Christopher K. Glass
Summary: The study evaluated how genetic variations in five inbred strains of mice influence macrophage responses to interleukin-4 (IL-4), revealing strain-specific patterns in gene expression induced by IL-4. Through deep learning and motif mutation analysis, the dominant combinations of transcription factors driving IL-4 enhancer activation were identified in macrophages from each strain.
Article
Cell Biology
Rafael Deliz-Aguirre, Fakun Cao, Fenja H. U. Gerpott, Nichanok Auevechanichkul, Mariam Chupanova, YeVin Mun, Elke Ziska, Marcus J. Taylor
Summary: Oligomerization of MyD88 is inducible and initially reversible. Formation of larger, stable oligomers triggers sequential recruitment of IRAK4 and IRAK1, with IRAK4 controlling MyD88 oligomer size and growth. MyD88 oligomer size functions as a physical threshold to trigger downstream signaling pathways.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Immunology
Heena Khan, Annu Bangar, Amarjot Kaur Grewal, Puneet Bansal, Thakur Gurjeet Singh
Summary: Caspases play a crucial role in neuronal disorders and neurodegenerative diseases, and the development of caspase inhibitors as therapeutic agents is being actively studied. However, no drug targeting caspase inhibition is currently available in the market.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Cell Biology
Wendy Leung, Antoine Simoneau, Sneha Saxena, Jessica Jackson, Parasvi S. Patel, Mangsi Limbu, Alessandro Vindigni, Lee Zou
Summary: The ATR kinase protects genomic integrity during S phase, and it employs distinct mechanisms to safeguard ongoing and new replication forks. ATR inhibitor enhances nascent DNA degradation at ongoing forks by MRE11 and EXO1, as well as exposes template ssDNA through fork uncoupling. It also triggers template DNA degradation by MRE11, CtIP, and EXO1 at new forks, leading to the exposure of nascent ssDNA.
Article
Cell Biology
Jinthe Van Loenhout, Laurie Freire Boullosa, Delphine Quatannens, Jorrit De Waele, Celine Merlin, Hilde Lambrechts, Ho Wa Lau, Christophe Hermans, Abraham Lin, Filip Lardon, Marc Peeters, Annemie Bogaerts, Evelien Smits, Christophe Deben
Summary: The study demonstrates that a combination therapy using auranofin and cold atmospheric plasma enhances the efficacy of oxidative stress-inducing therapy for glioblastoma, by modulating levels of reactive oxygen species and inhibiting the antioxidant system, inducing various cell death mechanisms to inhibit tumor growth and prolong survival.
Article
Behavioral Sciences
Cesar F. Lima, Patricia Arriaga, Andrey Anikin, Ana Rita Pires, Sofia Frade, Leonor Neves, Sophie K. Scott
Summary: The study found that listening to laughter elicited stronger facial responses than listening to crying, and these responses were also influenced by emotional authenticity. Authentic laughter triggered more activity in facial muscles and skin conductance responses than posed laughter. Stronger responses in the orbicularis and corrugator were related to perceived authenticity of laughter.
Article
Biochemistry & Molecular Biology
Souvik Ghosh, Meric Ataman, Maciej Bak, Anastasiya Borsch, Alexander Schmidt, Katarzyna Buczak, Georges Martin, Beatrice Dimitriades, Christina J. Herrmann, Alexander Kanitz, Mihaela Zavolan
Summary: The mammalian cleavage factor I (CFIm) plays a crucial role in alternative polyadenylation (APA). Our study revealed that changes in CFIm expression levels result in coherent APA alterations in over 800 genes, which cluster in distinct functional classes related to protein metabolism. Furthermore, CFIm regulates the biogenesis and repressive activity of miRNAs through APA. Our findings provide a comprehensive assessment of CFIm's role in integrating RNA processing with other cellular activities and shed light on the downstream signaling pathways elicited by CFIm.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Sara L. Banerjee, Frederic Lessard, Francois J. M. Chartier, Kevin Jacquet, Ana Osornio-Hernandez, Valentine Teyssier, Karim Ghani, Noemie Lavoie, Josee N. Lavoie, Manuel Caruso, Patrick Laprise, Sabine Elowe, Jean-Philippe Lambert, Nicolas Bisson
Summary: This study unravels the signaling networks of EPHRs in regulating cellular phenotypes by identifying protein complexes and their interactions. The results show that EPHRs directly phosphorylate PAR-3 and recruit CSK, which are crucial for cell sorting.
Editorial Material
Genetics & Heredity
Ivona Aksentijevich
Summary: Immune responses require a delicate balance - too weak or too strong a response can cause issues. Spleen tyrosine kinase plays a crucial role in multiple signaling pathways, and its gain-of-function alterations can lead to various problems, including hypogammaglobulinemia and predisposition to B cell lymphoma.
Article
Cell Biology
Anu S. Nath, Brendon D. Parsons, Stephanie Makdissi, Rebecca L. Chilvers, Yizhu Mu, Ceileigh M. Weaver, Irene Euodia, Katherine A. Fitze, Juyang Long, Michal Scur, Duncan P. Mackenzie, Andrew P. Makrigiannis, Nicolas Pichaud, Luc H. Boudreau, Andrew J. Simmonds, Christine A. Webber, Beata Derfalvi, Yannick Hammon, Richard A. Rachubinski, Francesca Di Cara
Summary: Peroxisomes play key roles in lipid metabolism and immune function, particularly in macrophage activation and cytoskeletal remodeling. Loss of peroxisome function can hinder host survival after infection.
Article
Cell Biology
Kanzo Suzuki, Ji-Woon Kim, Elena Nosyreva, Ege T. Kavalali, Lisa M. Monteggia
Summary: Acute inhibition of eEF2K activity induces rapid synaptic scaling in the hippocampus, while RA signaling pathway can also elicit similar synaptic scaling independently of eEF2K function. Activation of RAR alpha by retinoic acid leads to rapid antidepressant effects similar to ketamine.
Article
Pathology
Sridhar T. Narla, Daniel S. Bushnell, Joanne L. Duara, Carlton M. Bates
Summary: Keratinocyte growth factor (KGF) activates AKT in bladder urothelium, providing cytoprotection from cyclophosphamide. The study shows that KGF modifies AKT targets, suppresses apoptosis, and stabilizes mTORC1 signaling. AKT signaling is necessary for KGF-driven cytoprotection, and direct AKT activation blocks apoptosis. Thus, AKT may be a therapeutic target for preventing urothelial apoptosis.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Cell Biology
Julian R. Smith, Jack W. Dowling, Matthew I. McFadden, Andrew Karp, Johannes Schwerk, Joshua J. Woodward, Ram Savan, Adriana Forero
Summary: Cellular stress can activate signaling cascades to elicit inflammatory responses. This study investigates the role of the transcription factor MEF2A in regulating transcriptional stress responses and preventing R-loop accumulation. Loss of MEF2A leads to activation of the ATR kinase, which positively regulates R-loop-associated inflammatory responses.
Article
Medicine, Research & Experimental
Lucia Zhu, Diana Retana, Pedro Garcia-Gomez, Laura Alvaro-Espinosa, Neibla Priego, Mariam Masmudi-Martin, Natalia Yebra, Lauritz Miarka, Elena Hernandez-Encinas, Carmen Blanco-Aparicio, Sonia Martinez, Cecilia Sobrino, Nuria Ajenjo, Maria-Jesus Artiga, Eva Ortega-Paino, Raul Torres-Ruiz, Sandra Rodriguez-Perales, Riccardo Soffietti, Luca Bertero, Paola Cassoni, Tobias Weiss, Javier Munoz, Juan Manuel Sepulveda, Pedro Gonzalez-Leon, Luis Jimenez-Roldan, Luis Miguel Moreno, Olga Esteban, Angel Perez-Nunez, Aurelio Hernandez-Lain, Oscar Toldos, Yolanda Ruano, Lucia Alcazar, Guillermo Blasco, Jose Fernandez-Alen, Eduardo Caleiras, Miguel Lafarga, Diego Megias, Osvaldo Grana-Castro, Carolina Nor, Michael D. Taylor, Leonie S. Young, Damir Vareslija, Nicola Cosgrove, Fergus J. Couch, Lorena Cusso, Manuel Desco, Silvana Mouron, Miguel Quintela-Fandino, Michael Weller, Joaquin Pastor, Manuel Valiente
Summary: We report a medium-throughput drug-screening platform based on organotypic cultures that evaluates inhibitors against metastases growing in situ. Through this approach applied to brain metastasis, vulnerabilities were identified and a blood-brain barrier permeable HSP90 inhibitor was found to be effective against mouse and human brain metastases. In situ proteomic analysis revealed a novel molecular program in brain metastasis and potential biomarkers of poor prognosis and resistance mechanisms. This study validates METPlatform as a potent resource for metastasis research and personalized management of metastatic disease.
EMBO MOLECULAR MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Amanda Garrido, Eunjeong Kim, Ana Teijeiro, Paula Sanchez Sanchez, Rosa Gallo, Ajay Nair, Maria Matamala Montoya, Cristian Perna, Guillermo P Vicent, Javier Munoz, Ramon Campos-Olivas, Johannes C. Melms, Benjamin Izar, Robert F. Schwabe, Nabil Djouder
Summary: This study reveals the critical role of MCRS1 in the pathogenesis of cirrhosis, shedding light on potential new treatment strategies for the disease.
JOURNAL OF HEPATOLOGY
(2022)
Article
Chemistry, Medicinal
Vanesa Nozal, Loreto Martinez-Gonzalez, Marta Gomez-Almeria, Claudia Gonzalo-Consuegra, Paula Santana, Apirat Chaikuad, Eva Perez-Cuevas, Stefan Knapp, Daniel Lietha, David Ramirez, Sabrina Petralla, Barbara Monti, Carmen Gil, Angeles Martin-Requero, Valle Palomo, Eva de Lago, Ana Martinez
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the aggregation of protein TDP-43. In this study, TTBK1 inhibitors were identified as a promising therapeutic strategy for ALS. The novel pyrrolopyrimidine derivatives demonstrated their ability to reduce TDP-43 phosphorylation and preserve motor neurons in mouse models, suggesting their potential for future ALS therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biology
Belen Chaves-Arquero, Santiago Martinez-Lumbreras, Sergio Camero, Clara M. Santiveri, Yasmina Mirassou, Ramon Campos-Olivas, Maria Angeles Jimenez, Olga Calvo, Jose Manuel Perez-Canadillas
Summary: Heterodimerization of RNA binding proteins Nrd1 and Nab3 is crucial for yeast cell fitness, and the structure of Nrd1-Nab3 resembles that of Rna14/Rna15 despite sequence and evolutionary differences.
LIFE SCIENCE ALLIANCE
(2022)
Review
Cell Biology
Johanne Le Coq, Ivan Acebron, Barbara Rodrigo Martin, Pilar Lopez Navajas, Daniel Lietha
Summary: In this review, the authors discuss the role of focal adhesion kinase (FAK) in cell-matrix adhesion and migration. They highlight the known structural features of FAK and the challenges in understanding its integration in the focal adhesion complex and the structural changes during focal adhesion maturation.
JOURNAL OF CELL SCIENCE
(2022)
Article
Immunology
Almudena Chaves-Perez, Karla Santos-de-Frutos, Sergio de la Rosa, Irene Herranz-Montoya, Cristian Perna, Nabil Djouder
Summary: This study reveals the important role of transit-amplifying cells in controlling inflammatory signals and R-spondin production, which are essential for maintaining intestinal stem cell proliferation and tissue regeneration.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Sara Garcia-Alonso, Pablo Mesa, Laura de la Puente Ovejero, Gonzalo Aizpurua, Carmen G. Lechuga, Eduardo Zarzuela, Clara M. Santiveri, Manuel Sanclemente, Javier Munoz, Monica Musteanu, Ramon Campos-Olivas, Jorge Martinez-Torrecuadrada, Mariano Barbacid, Guillermo Montoya
Summary: This study describes the structure of the RAF1 protein in complex with HSP90 and CDC37. The research reveals that CDC37 can differentiate between different members of the RAF family. Additionally, the study shows that folded RAF1 assembles with 14-3-3 dimers, and disrupting the interaction between CDC37 and RAF1 may have potential therapeutic implications.
Article
Biochemistry & Molecular Biology
Belen Sanz-Castillo, Begona Hurtado, Diana Vara-Ciruelos, Aicha El Bakkali, Dario Hermida, Beatriz Salvador-Barbero, Diego Martinez-Alonso, Jose Gonzalez-Martinez, Clara Santiveri, Ramon Campos-Olivas, Pilar Ximenez-Embun, Javier Munoz, Monica Alvarez-Fernandez, Marcos Malumbres
Summary: This study reveals that the cell cycle kinase MASTL/Greatwall inhibits the activity of the PI3K-AKT signaling pathway by phosphorylating the PP2A/B55 inhibitor ENSA/ARPP19, thus limiting AKT activity. Furthermore, the study finds that MASTL is directly phosphorylated by mTORC1, which limits the dephosphorylation of IRS1 and GRB10 downstream of mTORC1, further restraining AKT activity. This research highlights the importance of the MASTL-PP2A/B55 kinase-phosphatase module in controlling AKT and maintaining metabolic homeostasis.
Editorial Material
Multidisciplinary Sciences
Tatiana P. Grazioso, Nabil Djouder
Summary: In their latest article, Seki and colleagues investigate the potential role of cold exposure in treating various cancer types, including untreatable ones like pancreatic cancer. They suggest that cold exposure may suppress tumor growth by activating brown adipose tissue (BAT), which dissipates heat through non-shivering thermogenesis. This leads to decreased circulating blood glucose, limiting tumor glucose uptake and favoring BAT uptake for thermogenesis.
Review
Biochemistry & Molecular Biology
Carlos Martinez-Garay, Nabil Djouder
Summary: In recent years, dietary interventions have shown promise in cancer treatment by influencing metabolism, tumor growth, development, and therapeutic response. However, due to a lack of understanding in the mechanisms behind dietary therapeutics, they are often overlooked as a potential line of cancer treatment. This review aims to provide a comprehensive overview of the anticancer effects of various diets and their development for clinical use, with the goal of establishing nutritional interventions as a standard treatment.
TRENDS IN MOLECULAR MEDICINE
(2023)
Review
Multidisciplinary Sciences
Tatiana P. Grazioso, Nabil Djouder
Summary: Cold therapy, a powerful therapeutic approach that has been used for centuries, has been largely forgotten in modern medicine. This review explores its history and potential application in treating various diseases, including cancer, through techniques like cryoablation, cryotherapy, cryoimmunotherapy, cryothalectomy, and cryogen agent delivery. Although clinical trials are limited, recent research shows promising results in experimental animal cancer models, highlighting the significance of further investigation.
Review
Oncology
Maria del Mar Rigual, Paula Sanchez Sanchez, Nabil Djouder
Summary: The liver, as the largest organ in mammals, has the ability to fully regenerate for tissue homeostasis. However, stress signals can impair liver regeneration and contribute to the development of hepatocellular carcinoma (HCC), a highly aggressive liver cancer. This review discusses the mechanisms of hepatic regeneration and their potential role in HCC development.
Meeting Abstract
Biophysics
Magnus S. Bauer, Sophia Gruber, Adina Hausch, Lukas F. Milles, Thomas Nicolaus, Leonard C. Schendel, Pilar Lopez Navajas, Erik Procko, Daniel Lietha, Rafael C. Bernardi, Jan Lipfert, Hermann E. Gaub
BIOPHYSICAL JOURNAL
(2022)