Article
Genetics & Heredity
Naotaka Ochi, Mai P. Nakamura, Rina Nagata, Naoki P. Wakasa, Ryosuke Nakano, Tatsushi P. Igaki
Summary: Cell competition is a context-dependent process where unfit cells are eliminated when confronted with fitter cells. Through genetic studies in Drosophila, it was found that ER stress leads to cell competition via upregulation of the bZIP transcription factor Xrp1, leading to reduced protein synthesis and cell death. These findings suggest that Xrp1-mediated phosphorylation of eIF2 alpha could be a common mechanism of cell competition triggered by different stimuli.
Article
Biochemistry & Molecular Biology
Zheng Xiao-ci, Wu Die, Xu Xin
Summary: This article summarizes the research progress on the eIF2 alpha kinase family and its possible role in renal diseases, providing a new theoretical basis and reference for the prevention and treatment of kidney diseases.
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Genetics & Heredity
William J. Andrews, Swagat Ray, Tatiana Panova, Christoph Engel, Konstantin Panov
Summary: The study found that DNA intercalators/groove binders can effectively inhibit Pol-I specific transcription without affecting its synthetic ability. These compounds have limited effect on transcription by Pol-II and III, demonstrating the hypersensitivity of Pol-I transcription. The research suggests that alterations in the 3D structure of the rDNA promoter may affect the stability of the pre-initiation complex and initiation.
Article
Oncology
Hao-Xuan Du, Hu Wang, Xiao-Peng Ma, Hao Chen, Ai-Bin Dai, Ke-Xiang Zhu
Summary: Pancreatic cancer is a deadly disease with a poor prognosis, and immunotherapy has become a new focus in tumor treatment. This study investigates the potential of EIF2AK2 as a diagnostic and prognostic marker for pancreatic cancer by analyzing its expression and identifying differentially expressed genes. The results suggest that EIF2AK2 may serve as a biomarker for pancreatic cancer diagnosis and prognosis, as well as a potential therapeutic target.
Article
Cell Biology
Junping Bao, Zhanyang Qian, Lei Liu, Xin Hong, Hui Che, Xiaotao Wu
Summary: The study reveals that the eIF2 alpha/ATF4/Ihh signaling pathway is involved in regulating ROS levels and apoptosis in NP cells, and disrupting this pathway may provide promising methods in preventing IDD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Wen Lu, Kun Ni, Zhuangzhuang Li, Lili Xiao, Yini Li, Yumeng Jiang, Jincheng Zhang, Haibo Shi
Summary: This study revealed that salubrinal, a dephosphorylation inhibitor of eIF2 alpha signaling, can protect against cisplatin-induced damage in cochlear cells by attenuating endoplasmic reticulum stress. These findings suggest that pharmacological inhibition of eIF2 alpha-mediated ERS could be a potential treatment for cisplatin-induced ototoxicity.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Microbiology
Heather A. Walters, Brenda H. Welter, Harrison C. Moss, Martha A. Villano, Ronny Orobio-Hurtado, William J. Sullivan, Lesly A. Temesvari
Summary: This study identified two eIF2 alpha kinases in E. invadens that may regulate the stress response of Entamoeba, including oxidative stress, stage conversion, and virulence.
Article
Cell Biology
Christina Skofler, Florian Kleinegger, Stefanie Krassnig, Anna Maria Birkl-Toeglhofer, Georg Singer, Holger Till, Martin Benesch, Regina Cencic, John A. Porco, Jerry Pelletier, Christoph Castellani, Andrea Raicht, Ewa Izycka-Swieszewska, Piotr Czapiewski, Johannes Haybaeck
Summary: The study found that eIF4AI is overexpressed in NB patient tissue, and treatment with CR-1-31-B results in decreased viability, increased apoptosis rates, and changes in cell cycle distribution in NB cell lines. CR-1-31-B is effective against NB cell lines at low nanomolar doses and does not affect non-malignant cells.
Article
Chemistry, Medicinal
Xintao Gao, Yonglong Jin, Wenyong Zhu, Xiaochen Wu, Jing Wang, Chuanlong Guo
Summary: eIF4E is a central regulator in cancer cell growth, but there are currently no clinically available eIF4E inhibitors. Interfering with eIF4E/eIF4G interactions may provide a new strategy for designing eIF4E inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Genetics & Heredity
Prakash Amruth Raj Chukka, Stacey D. Wetmore, Nehal Thakor
Summary: Translational control plays a crucial role in dictating gene expression and altering physiological processes in eukaryotic cells. eIF5B plays a significant role in this process, especially in the survival and drug resistance of cancer cells.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Yanhui Li, Jianhua Zhao, Zhikun Yuan, Dehan Yuan, Mao Fang, Minru Xie, Minghan Xia
Summary: The tumorigenesis of breast cancer is a complex process involving abnormal gene expression and dysregulation of eukaryotic initiation factor (eIF) subunits. In this study, the overexpression of eIF3b was found in breast cancer cell lines and tumor tissues, with higher expression in advanced stages and lymph node metastatic breast cancer. Moreover, eIF3b knockdown inhibited tumor growth, migration, and invasion, while overexpression had the opposite effects. Mechanistically, eIF3b downregulation suppressed breast cancer development through the Wnt/β-catenin pathway. In conclusion, eIF3b may serve as a potential therapeutic target for breast cancer treatment.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Oncology
Angela Rubio, Gavin D. Garland, Aristeidis Sfakianos, Robert F. Harvey, Anne E. Willis
Summary: Abnormalities in RNA binding proteins within the canonical translation factor machinery are associated with tumorigenesis and can be targeted for therapeutic purposes.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Shaoran Song, Jie Liu, Miao Zhang, Xiaoqian Gao, Wei Sun, Peijun Liu, Yaochun Wang, Juan Li
Summary: The expression of the EIF3 gene family is associated with prognosis in breast cancer and may serve as a therapeutic target.
Article
Oncology
Chengzhi Xu, Yupeng Shen, Yong Shi, Ming Zhang, Liang Zhou
Summary: This study reveals the role of EIF3B in head and neck squamous cell carcinoma (HNSCC) and identifies its promotion of CEBPB translation and IL6R expression. These findings provide important insights into the molecular basis and pathogenesis of HNSCC.
CANCER CELL INTERNATIONAL
(2022)
Article
Cell Biology
Thao Thi Dang, Mi-Jeong Kim, Yoon Young Lee, Hien Thi Le, Kook Hwan Kim, Somi Nam, Seung Hwa Hyun, Hong Lim Kim, Su Wol Chung, Hun Taeg Chung, Eek-Hoon Jho, Hiderou Yoshida, Kyoungmi Kim, Chan Young Park, Myung-Shik Lee, Sung Hoon Back
Summary: There are diverse links between macroautophagy/autophagy pathways and unfolded protein response (UPR) pathways under endoplasmic reticulum (ER) stress conditions. EIF2S1 phosphorylation plays an important role in regulating autophagy during ER stress by promoting nuclear translocation of TFEB and TFE3. Defects in EIF2S1 phosphorylation impair autophagic processes and hinder the restoration of ER homeostasis.
Article
Cell Biology
Sophia M. Hochrein, Hao Wu, Miriam Eckstein, Laura Arrigoni, Josip S. Herman, Fabian Schumacher, Christian Gerecke, Mathias Rosenfeldt, Dominic Gru, Burkhard Kleuser, Georg Gasteiger, Wolfgang Kastenmu, Bart Ghesquiere, Jan Van den Bossche, E. Dale Abel, Martin Vaeth
Summary: Metabolic reprogramming, specifically glycolytic reprogramming, plays a crucial role in activated T cells by regulating gene expression and pathogenicity. GLUT3 is essential for the effector functions of Th17 cells and its inhibition shows promise in mitigating Th17-cell-mediated inflammatory diseases.
Article
Immunology
Sabrina Daehling, Ana Maria Mansilla, Konrad Knoepper, Anika Grafen, Daniel T. Utzschneider, Milas Ugur, Paul G. Whitney, Annabell Bachem, Panagiota Arampatzi, Fabian Imdahl, Tsuneyasu Kaisho, Dietmar Zehn, Frederick Klauschen, Natalio Garbi, Axel Kallies, Antoine-Emmanuel Saliba, Georg Gasteiger, Sammy Bedoui, Wolfgang Kastenmueller
Summary: This study identifies the role of conventional dendritic cells 1 (cDC1s) in maintaining and protecting exhausted T cells (Tpex) within specific microenvironments in the spleen. cDC1s prevent overactivation of Tpex cells in other inflammatory environments and balance viral control, exhaustion, and immunopathology.
Article
Immunology
Constantin Rickassel, Ann-Christin Gnirck, Nikhat Shaikh, Virginia Adamiak, Alex Waterhoelter, Yakup Tanriver, Katrin Neumann, Tobias B. Huber, Georg Gasteiger, Ulf Panzer, Jan-Eric Turner
Summary: In this article, the authors provide a detailed analysis of the NCR+T-bet(+) ILC population in the murine kidney, identifying cNK cells and ILC1s as the two major subsets. The study shows that cNK cells and ILC1s are dispensable for the initiation and progression of immune-mediated glomerular disease. The authors also caution against the use of standard antibody depletion methods for studying NCR+ ILC function in mouse models.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Valeria Fumagalli, Valentina Venzin, Pietro Di Lucia, Federica Moalli, Xenia Ficht, Gioia Ambrosi, Leonardo Giustini, Francesco Andreata, Marta Grillo, Diletta Magini, Micol Rava, Christin Friedrich, Jason D. Fontenot, Philippe Bousso, Sarah A. Gilmore, Shahzada Khan, Manuel Baca, Eric Vivier, Georg Gasteiger, Mirela Kuka, Luca G. Guidotti, Matteo Iannacone
Summary: Group 1 innate lymphoid cells (ILCs) play a role in controlling T cell-mediated liver immunopathology by limiting local IL-2 concentration.
SCIENCE IMMUNOLOGY
(2022)
Article
Immunology
Alexandra Kupke, Asisa Volz, Erik Dietzel, Astrid Freudenstein, Joerg Schmidt, Hosam Shams-Eldin, Sylvia Jany, Lucie Sauerhering, Verena Kraehling, Michelle Gellhorn Serra, Christiane Herden, Markus Eickmann, Stephan Becker, Gerd Sutter
Summary: This study tested two recombinant MVA-based Ebola virus vaccine candidates in mice and found that vaccination generated virus-neutralizing antibodies and specific CD8+ T cell response. Vaccinated mice survived Ebola virus infection and had significantly reduced viral loads compared to mock-vaccinated mice.
Article
Multidisciplinary Sciences
Anahita Fathi, Christine Dahlke, Verena Krahling, Alexandra Kupke, Nisreen M. A. Okba, Matthijs P. Raadsen, Jasmin Heidepriem, Marcel A. Muller, Grigori Paris, Susan Lassen, Michael Kluver, Asisa Volz, Till Koch, My L. Ly, Monika Friedrich, Robert Fux, Alina Tscherne, Georgia Kalodimou, Stefan Schmiedel, Victor M. Corman, Thomas Hesterkamp, Christian Drosten, Felix F. Loeffler, Bart L. Haagmans, Gerd Sutter, Stephan Becker, Marylyn M. Addo
Summary: A booster vaccination with MVA-MERS-S is safe and significantly improves immunity to the Middle East Respiratory Syndrome coronavirus.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Stephanie Riederer, Ana del Canizo, Javier Navas, Marlowe G. Peter, Ellen K. Link, Gerd Sutter, Juan J. Rojas
Summary: It was found that the B2 nuclease in vaccinia viruses inhibits the cGAS signaling pathway activated by cytoplasmic viral replication. Deletion of the B2R gene enhances the antitumor activity and immune response against tumor antigens in tumor cells infected with vaccinia viruses.
CANCER GENE THERAPY
(2023)
Article
Virology
Georgia Kalodimou, Sylvia Jany, Astrid Freudenstein, Jan Hendrik Schwarz, Leonard Limpinsel, Cornelius Rohde, Alexandra Kupke, Stephan Becker, Asisa Volz, Alina Tscherne, Gerd Sutter
Summary: The COVID-19 pandemic has had significant impacts on human health and the economy. Vaccines are crucial for controlling the pandemic in the future. In this study using mice, it was found that the MVA-SARS-2-ST vaccine induced stronger immune responses compared to the MVA-SARS-2-S vaccine in both short- and long-interval immunization schedules.
Article
Cell Biology
Manuel O. Jakob, Daniel Spari, Daniel Sanchez Taltavull, Lilian Salm, Bahtiyar Yilmaz, Remi Doucet Ladeveze, Catherine Mooser, David Pereyra, Ye Ouyang, Theresa Schmidt, Irene Mattiola, Patrick Starlinger, Deborah Stroka, Franziska Tschan, Daniel Candinas, Georg Gasteiger, Christoph S. N. Klose, Andreas Diefenbach, Mercedes Gomez de Agueero, Guido Beldi
Summary: It is commonly believed that surgical infections are primarily caused by environmental or cutaneous bacteria. Accordingly, efforts to prevent postoperative infections have focused on improving hygiene and asepsis. However, our study revealed that the main causative bacteria in postoperative infections are of intestinal origin, which was also confirmed in mice undergoing partial hepatectomy. We found that CCR6+ group 3 innate lymphoid cells (ILC3s) play a crucial role in limiting systemic bacterial spread, and this function is dependent on the production of interleukin-22 (IL-22) and the expression of antimicrobial peptides in hepatocytes. Our findings highlight the significance of endogenous intestinal bacteria as a source of postoperative infection and suggest that ILC3s could be potential therapeutic targets.
Article
Immunology
Lucas Wilken, Sonja Stelz, Ayse Agac, Gerd Sutter, Chittappen Kandiyil Prajeeth, Guus F. Rimmelzwaan
Summary: The four serotypes of dengue virus (DENV1-4) remain a major public health threat. The first licensed dengue vaccine has shown poor performance in individuals with low immunity, making them susceptible to antibody-enhanced dengue disease. NS1, a non-structural protein of DENV, has the potential to trigger vascular leakage, a severe symptom of dengue disease, but its use as a vaccine antigen is hindered by this drawback.
Article
Gastroenterology & Hepatology
Julia Sacherl, Anna D. Kosinska, Kristina Kemter, Martin Kaechele, Sabine C. Laumen, Helene A. Kerth, Edanur Ates Oez, Lisa S. Wolff, Jinpeng Su, Sandra Essbauer, Gerd Sutter, Martin Scholz, Katrin Singethan, Jens Altrichter, Ulrike Protzer
Summary: The aim of the study was to find an optimal combination to stabilize and enhance the immunogenicity of the protein and vector components in the vaccine. The results showed that the stabilized vaccine was able to effectively induce immune responses and maintain stability under high temperature storage. This study is of great significance for global vaccine applications and vaccine development.
Article
Immunology
Milas Ugur, R. Jacob Labios, Chloe Fenton, Konrad Knoepper, Katarzyna Jobin, Fabian Imdahl, Gosia Golda, Kathrin Hoh, Anika Grafen, Tsuneyasu Kaisho, Antoine-Emmanuel Saliba, Dominic Gruen, Georg Gasteiger, Marc Bajenoff, Wolfgang Kastenmueller
Summary: This study discovered specific anatomical niches in lymph nodes where preDCs differentiate into immature cDCs. These niches, located in the medullary cords of the lymph nodes, play a role in the development of the cDC1 network. During inflammation, the network can be temporarily impaired, but can be restored by regulating the local density of cDC1s.
Article
Gastroenterology & Hepatology
Knud Esser, Xiaoming Cheng, Jochen M. Wettengel, Julie Lucifora, Lea Hansen-Palmus, Katharina Austen, Armando A. Roca Suarez, Sarah Heintz, Barbara Testoni, Firat Nebioglu, Minh Tu Pham, Shangqing Yang, Alma Zernecke, Dirk Wohlleber, Marc Ringelhan, Mathias Broxtermann, Daniel Hartmann, Norbert Hueser, Julia Mergner, Andreas Pichlmair, Wolfgang E. Thasler, Mathias Heikenwalder, Georg Gasteiger, Andreas Blutke, Axel Walch, Percy A. Knolle, Ralf Bartenschlager, Ulrike Protzer
Summary: Hepatitis B virus (HBV) can enter hepatocytes by binding with lipoproteins and utilize the cholesterol transport pathway of macrophages to deliver itself to hepatocytes. This transmission through the lipid transport pathway to the liver may involve transinfection of liver macrophages and result in deposition of HBV in the perisinusoidal space.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Medicine, Research & Experimental
Christian Meyer zu Natrup, Alina Tscherne, Christine Dahlke, Malgorzata Ciurkiewicz, Dai-Lun Shin, Anahita Fathi, Cornelius Rohde, Georgia Kalodimou, Sandro Halwe, Leonard Limpinsel, Jan H. Schwarz, Martha Klug, Meral Esen, Nicole Schneiderhan-Marra, Alex Dulovic, Alexandra Kupke, Katrin Brosinski, Sabrina Clever, Lisa-Marie Schuenemann, Georg Beythien, Federico Armando, Leonie Mayer, Marie L. Weskamm, Sylvia Jany, Astrid Freudenstein, Tamara Tuchel, Wolfgang Baumgaertner, Peter Kremsner, Rolf Fendel, Marylyn M. Addo, Stephan Becker, Gerd Sutter, Asisa Volz
Summary: The study found that infection with a stable version of SARS-CoV-2 S protein resulted in higher levels of S1 protein on the cell surface, which was beneficial for inducing protective antibody levels. Mice vaccinated with this vaccine generated a large amount of broadly reactive anti-S antibodies that effectively neutralized different SARS-CoV-2 variants. These vaccinated mice also showed strong immune responses and protection from disease and severe lung pathology upon challenge infection.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Cell Biology
Leonie M. Weskamm, Anahita Fathi, Matthijs P. Raadsen, Anna Z. Mykytyn, Till Koch, Michael Spohn, Monika Friedrich, Bart L. MVA MERS S Study Grp, Bart L. Haagmans, Stephan Becker, Gerd Sutter, Christine Dahlke, Marylyn M. Addo
Summary: This study analyzes the long-term immune response to the MVA-MERS-S vaccine and finds that a late booster immunization can enhance antibody and B cell immunity against MERS-CoV. These findings may be relevant for COVID-19 vaccination strategies.
CELL REPORTS MEDICINE
(2022)