Article
Immunology
Jonas Johannes Papendorf, Frederic Ebstein, Sara Alehashemi, Daniela Gerent Petry Piotto, Anna Kozlova, Maria Teresa Terreri, Anna Shcherbina, Andre Rastegar, Marta Rodrigues, Renan Pereira, Sophia Park, Bin Lin, Kat Uss, Sophie Moeller, Ana Flavia da Silva Pina, Flavio Sztajnbok, Sofia Torreggiani, Julie Niemela, Jennifer Stoddard, Sergio D. Rosenzweig, Andrew J. Oler, Colton McNinch, Marietta M. de Guzman, Adriana Fonseca, Nicole Micheloni, Melissa Mariti Fraga, Sandro Felix Perazzio, Raphaela Goldbach-Mansky, Adriana A. de Jesus, Elke Krueger
Summary: Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers cause CANDLE/PRAAS, a recurring autoinflammatory disease. This study identified novel genetic variants in patients with CANDLE/PRAAS, expanding the spectrum of associated mutations and improving genetic diagnosis and counseling.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
M. Cecilia Poli
Summary: Inborn errors of immunity (IEI) or primary immune deficiencies (PIDD) are caused by genetic variants that affect molecules relevant to the immune response. Defects in over 450 genes have been identified as causes of IEI, leading to various clinical manifestations. This review focuses on IEI associated with mutations affecting the proteasome, describing their clinical, genetic, and molecular aspects, as well as the contribution of these studies in determining therapeutic interventions.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Clinical Neurology
Carolina Bianchi, Beatriz Alvarez-Castelao, Alvaro Sebastian-Serrano, Caterina Di Lauro, Lucia Soria-Tobar, Annette Nicke, Tobias Engel, Miguel Diaz-Hernandez
Summary: Recent evidence suggests a causal relationship between neurofibrillary tangles (NFTs) formation and UPS dysfunction in tauopathies, including Alzheimer's disease (AD). This study investigates the impact of ATP, a danger-associated molecule pattern (DAMP) associated with neuroinflammation, on AD-associated UPS dysfunction.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Karthik Selvaraju, Kourosh Lotfi, Johannes Gubat, Maria Miquel, Amanda Nilsson, Julia Hill, Lasse D. Jensen, Stig Linder, Padraig D'Arcy
Summary: The dienone compound VLX1570 exhibits tumor cell selectivity, targeting the ubiquitin-proteasome system (UPS) in acute myeloid leukemia (AML) cells. It induces ER stress, accumulation of ubiquitin complexes, and loss of cell viability in a dose-dependent manner, with Caspase activation but not glutathione depletion correlating to sensitivity.
Review
Medicine, General & Internal
Carl Christoph Goetzke, Frederic Ebstein, Tilmann Kallinich
Summary: The UPS plays a crucial role in cellular functions, such as regulating protein homeostasis and MHC I antigen processing. In humans, loss-of-function mutations in the proteasome can lead to autoinflammation, while abnormally increased proteasomal activity is also linked to other inflammatory diseases.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Min Qiu, Jimei Chen, Xiaohong Li, Jian Zhuang
Summary: Cardiovascular diseases (CVDs) are a major social problem worldwide, and oxidative stress plays a vital role in CVDs. The ubiquitin-proteasome system (UPS) is associated with oxidative stress and affects the development of CVDs. This review provides a comprehensive analysis of the roles of UPS and oxidative stress in CVDs, suggesting new targets for the treatment and prevention of CVDs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Fang Liang, Weixiao Qin, Yilan Zeng, Dan Wang
Summary: Autoimmune diseases and autoinflammatory diseases are two types of immune system disorders, and pyroptosis plays a crucial role in these diseases. Gasdermins, a pore-forming protein mainly expressed in immune cells, gastrointestinal tract, and skin, are considered as the executors of pyroptosis and have various functions and pathological effects such as pro-inflammatory responses, immune activation, and tumor mediation. Recent studies have demonstrated the significant role of gasdermins in autoimmune diseases, autoinflammatory diseases, and immune-related neoplastic diseases, making them potential therapeutic targets for immune disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Liuting Zeng, Kailin Yang, Tianqing Zhang, Xiaofei Zhu, Wensa Hao, Hua Chen, Jinwen Ge
Summary: Autoimmunity is a complex mechanism involving various cell types, and its understanding has been limited. However, the emergence of single-cell transcriptome sequencing technology has provided a novel approach to study autoimmune diseases. By analyzing cells independently, this technology can provide unbiased results and more mRNA information for identifying cell sub-populations, ultimately leading to a better understanding of the molecular pathways involved in autoimmune diseases and the development of targeted drugs.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Immunology
Monica Gelzo, Alice Castaldo, Antonietta Giannattasio, Giulia Scalia, Maddalena Raia, Maria Valeria Esposito, Marco Maglione, Stefania Muzzica, Carolina D'Anna, Michela Grieco, Vincenzo Tipo, Antonio La Cava, Giuseppe Castaldo
Summary: This study analyzed the immunological, cellular, and genetic characteristics of children with MIS-C. The results showed significant differences in serum cytokines, lymphocyte populations, and genetic variations among MIS-C patients, which helps improve the understanding of the disease's pathogenesis and provides insights for diagnosis and treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Srirupa Bhattacharyya, Janet L. Oblinger, Roberta L. Beauchamp, Zhenzhen Yin, Serkan Erdin, Priya Koundinya, Anna D. Ware, Marc Ferrer, Justin T. Jordan, Scott R. Plotkin, Lei Xu, Long-Sheng Chang, Vijaya Ramesh
Summary: This study identifies a class of compounds targeting the ubiquitin-proteasome pathway (UPP) that have potent efficacy in treating NF2-associated tumors. These compounds reduce cell viability and induce apoptosis by downregulating c-KIT and PDGFR alpha expression and upregulating genes associated with endoplasmic reticulum stress-mediated activation of the unfolded protein response (UPR). In vivo models further demonstrate the therapeutic potential of these drugs.
Review
Immunology
Niraj Parihar, Lokesh Kumar Bhatt
Summary: The ubiquitin-proteasome pathway plays a crucial role in the development of autoimmune diseases, with DUBs regulating protein ubiquitination to influence immune responses.
INFLAMMOPHARMACOLOGY
(2021)
Article
Immunology
Jie Song, Muyuan Li, Caiyan Li, Ke Liu, Yaxi Zhu, Huali Zhang
Summary: This review provides a basic understanding of RLR biology, summarizes recent findings on the regulatory mechanisms of RLR signaling cascade, and focuses on the relationship between RLRs and diseases such as SARS-CoV-2, malaria, bacterial infections, autoimmune diseases, and anti-tumor immunity. These findings offer insights and guidance for antiviral and immunomodulatory therapies targeting RLRs.
AUTOIMMUNITY REVIEWS
(2022)
Article
Multidisciplinary Sciences
Xiao Yang, Meihui Song, Ying Wang, Taicong Tan, Zhongyu Tian, Binyuan Zhai, Xuan Yang, Yingjin Tan, Yanding Cao, Shaojun Dai, Shunxin Wang, Liangran Zhang
Summary: This study identifies a molecular pathway for axis length regulation in meiotic cells. It shows that the cohesin regulator Pds5 interacts with proteasomes to regulate the ubiquitination level of chromosome proteins, which affects chromosome axis length. Two ubiquitin E3 ligases, SCF and Ufd4, are involved in this pathway. These findings contribute to our understanding of how Pds5 regulates meiotic chromosome organization and suggest a conserved regulatory mechanism in higher eukaryotes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Plant Sciences
Dania P. Lobaina, Roberto Tarazi, Tamara Castorino, Maite F. S. Vaslin
Summary: The ubiquitin-proteasome system (UPS) is crucial for maintaining cellular balance and plays a key role in DNA repair, gene transcription, and protein activation. Viruses often manipulate the UPS to maintain viral protein levels and evade host defenses. Understanding the mechanisms used by plant viruses to subvert host defenses is important for developing biotechnological approaches for viral resistance.
Article
Immunology
Ewa Wiesik-Szewczyk, Marcin Zietkiewicz, Agata Bedzichowska, Katarzyna Napiorkowska-Baran, Aleksandra Matyja-Bednarczyk, Anna Felis-Giemza, Karina Jahnz-Rozyk
Summary: This study investigated the willingness of immunodeficient patients on biologic therapy to accept vaccination against SARS-CoV-2. The results showed that 81% of the patients were vaccinated, and 82% were willing to receive a booster dose. The hesitant patients doubted the vaccine's safety, feared a post-vaccination disease flare, and had primary or vocational education.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Caroline Perner, Elke Krueger
Summary: Neuronal cells are specialized in rapid transfer and translation of information. The endoplasmic reticulum plays a fundamental role in providing the necessary requirements for optimal neuronal function. Accumulation of misfolded proteins in the ER lumen, along with other external stimuli, can induce ER stress and trigger a stress response to restore cellular homeostasis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Nienke Willemsen, Isabel Arigoni, Maja Studencka-Turski, Elke Krueger, Alexander Bartell
Summary: Regulation of proteasomal activity is crucial for cellular proteostasis and function. This study investigates the role of proteasome subunits Psmb4 and Psmb8 in brown adipocyte differentiation, function, and proteostasis. The findings suggest that Psmb4 is required for adipocyte development and function, and its loss disrupts proteostasis and impairs adipogenesis. Atf3 is identified as a key effector of inflammation and blocking adipogenesis. Additionally, the study highlights the involvement of Nfe2l1 in maintaining proteostasis under these conditions.
MOLECULAR METABOLISM
(2022)
Review
Cell Biology
Jonas Johannes Papendorf, Elke Krueger, Frederic Ebstein
Summary: Proteostasis refers to the ability of cells to maintain a stable proteome through protein synthesis, quality control, and degradation. Disorders caused by proteostasis perturbations are increasingly being identified, and they often exhibit an autoinflammatory component. This review provides an overview of the molecular pathogenesis of these disorders and summarizes the mechanisms by which impaired proteostasis promotes autoinflammation.
Letter
Clinical Neurology
Lena-Luise Becker, Frederic Ebstein, Denise Horn, Christos C. Zouboulis, Elke Krueger, Angela M. Kaindl
Letter
Dermatology
Alban Ziegler, Frederic Ebstein, Hanan Shamseldin, Clement Prouteau, Elke Krueger, Yousef M. Binamer, Dominique Bonneau, Fowzan S. Alkuraya, Ludovic Martin
Summary: Keratinocyte differentiation factor 1 (KDF1) is associated with hidradenitis suppurativa and ectodermal dysplasia. A new variant of KDF1 (p.His254Tyr) has been found in a 20-year-old male patient with hidradenitis suppurativa and ectodermal dysplasia. The variant actually causes pathogenic gain-of-function of KDF1 through upregulation of IKK alpha.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Article
Cell Biology
Frederic Ebstein, Sebastien Kuery, Victoria Most, Cory Rosenfelt, Marie-Pier Scott-Boyer, Geeske M. van Woerden, Thomas Besrard, Jonas Johannes Papendorf, Maja Studencka-Turski, Tianyun Wang, Tzung-Chien Hsieh, Richard Golnik, Dustin Baldridge, Cara Forster, Charlotte de Konink, Selina M. W. Teurlings, Virginie Vignard, Richard H. van Jaarsveld, Lesley Ades, Benjamin Cogne, Cyril Mignot, Wallid Deb, Marjolijn C. J. Jongmans, F. Sessions Cole, Marie-Jose H. van den Boogaard, Jennifer A. Wambach, Daniel J. Wegner, Sandra Yang, Vickie Hannig, Jennifer Ann Brault, Neda Zadeh, Bruce Bennetts, Boris Keren, Anne-Claire Gelineau, Zoee Powis, Meghan Towne, Kristine Bachman, Andrea Seeley, Anita E. Beck, Jennifer Morrison, Rachel Westman, Kelly Averill, Theresa Brunet, Judith Haasters, Melissa T. Carter, Matthew Osmond, Patricia G. Wheeler, Francesca Forzano, Shehla Mohammed, Yannis Trakadis, Andrea Accogli, Rachel Harrison, Yiran Guo, Hakon Hakonarson, Sophie Rondeau, Genevieve Baujat, Giulia Barcia, Rene Guenther Feichtinger, Johannes Adalbert Mayr, Martin Preisel, Frederic Laumonnier, Tilmann Kallinich, Alexej Knaus, Bertrand Isidor, Peter Krawitz, Uwe Voelker, Elke Hammer, Arnaud Droit, Evan E. Eichler, Ype Elgersma, Peter W. Hildebrand, Francois Bolduc, Elke Krueger, Stephane Bezieau
Summary: This study identified mutations in the PSMC3 gene that are associated with protein homeostasis dysfunction, leading to neurodevelopmental delay and intellectual disability. The mutations affected dendrite development in neurons and impaired learning capabilities in fruit flies, potentially through disruption of protein translocation and induction of proteotoxic stress. The findings suggest a potential link between protein homeostasis dysfunction and neurodevelopmental disorders, opening up new avenues for further research.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Correction
Multidisciplinary Sciences
Julia Reichelt, Wiebke Sachs, Sarah Frombling, Julia Fehlert, Maja Studencka-Turski, Anna Betz, Desiree Loreth, Lukas Blume, Susanne Witt, Sandra Pohl, Johannes Brand, Maire Czesla, Jan Knop, Bogdan I. Florea, Stephanie Zielinski, Marlies Sachs, Elion Hoxha, Irm Hermans-Borgmeyer, Gunther Zahner, Thorsten Wiech, Elke Kruger, Catherine Meyer-Schwesinger
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Julia Reichelt, Wiebke Sachs, Sarah Froembling, Julia Fehlert, Maja Studencka-Turski, Anna Betz, Desiree Loreth, Lukas Blume, Susanne Witt, Sandra Pohl, Johannes Brand, Maire Czesla, Jan Knop, Bogdan I. Florea, Stephanie Zielinski, Marlies Sachs, Elion Hoxha, Irm Hermans-Borgmeyer, Gunther Zahner, Thorsten Wiech, Elke Krueger, Catherine Meyer-Schwesinger
Summary: In membranous nephropathy, autoantibodies target podocytes of the kidney filter, resulting in injury. The authors found that the disturbances in protein stability and proteinuria are related to abnormal interactions between non-functional UCH-L1 enzyme and the proteasome, reducing its capacity. The mechanistic significance of the ubiquitin proteasome system (UPS) in a kidney autoimmune environment is not well understood.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Zeinab Waad Sadiq, Annamaria Brioli, Ruba Al-Abdulla, Gonca Cetin, Jacqueline Schuett, Hugo Murua Escobar, Elke Krueger, Frederic Ebstein
Summary: This study investigates the effects of protein homeostasis disruptors on multiple myeloma cells and shows that inhibition of protein de-ubiquitination can induce immunogenic cell death, suggesting a new therapeutic strategy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Angelique Sanchez Dafun, Dusan Zivkovic, Stephen Adonai Leon-Icaza, Sophie Moeller, Carine Froment, Delphine Bonnet, Adriana Almeida de Jesus, Laurent Alric, Muriel Quaranta-Nicaise, Audrey Ferrand, Celine Cougoule, Etienne Meunier, Odile Burlet-Schiltz, Frederic Ebstein, Raphaela Goldbach-Mansky, Elke Krueger, Marie-Pierre Bousquet, Julien Marcoux
Summary: The mammalian 20S catalytic core of the proteasome is composed of 14 different subunits and exists as different subtypes depending on cell type. Proteasome activity is altered by post-translational modifications and genetic variants. A new miniaturized workflow combining top-down and bottom-up mass spectrometry is presented for analyzing proteasome assembly status and full proteoform footprint.
Article
Biochemistry & Molecular Biology
Simone Venz, Viola von Bohlen Und Halbach, Christian Hentschker, Heike Junker, Andreas Walter Kuss, Thomas Sura, Elke Krueger, Uwe Voelker, Oliver von Bohlen Und Halbach, Lars Riff Jensen, Elke Hammer
Summary: A workflow for tandem mass spectrometry-based protein profiling of immunohistochemistry specimens was established and applied to tissue sections. The CA1 region of the hippocampus was investigated using protein extraction and digestion methods followed by mass spectrometry measurement and data analysis. Literature searches and Gene Ontology annotation verified the applicability of this method for global protein profiling using formalin-fixed and embedded material and previously used immunohistochemistry slides.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Jonas Johannes Papendorf, Frederic Ebstein, Sara Alehashemi, Daniela Gerent Petry Piotto, Anna Kozlova, Maria Teresa Terreri, Anna Shcherbina, Andre Rastegar, Marta Rodrigues, Renan Pereira, Sophia Park, Bin Lin, Kat Uss, Sophie Moeller, Ana Flavia da Silva Pina, Flavio Sztajnbok, Sofia Torreggiani, Julie Niemela, Jennifer Stoddard, Sergio D. Rosenzweig, Andrew J. Oler, Colton McNinch, Marietta M. de Guzman, Adriana Fonseca, Nicole Micheloni, Melissa Mariti Fraga, Sandro Felix Perazzio, Raphaela Goldbach-Mansky, Adriana A. de Jesus, Elke Krueger
Summary: Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers cause CANDLE/PRAAS, a recurring autoinflammatory disease. This study identified novel genetic variants in patients with CANDLE/PRAAS, expanding the spectrum of associated mutations and improving genetic diagnosis and counseling.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Frederic Ebstein, Sebastien Kuery, Victoria Most, Cory Rosenfelt, Marie-Pier Scott-Boyer, Geeske M. van Woerden, Thomas Besrard, Jonas Johannes Papendorf, Maja Studencka-Turski, Tianyun Wang, Tzung-Chien Hsieh, Richard Golnik, Dustin Baldridge, Cara Forster, Charlotte de Konink, Selina M. W. Teurlings, Virginie Vignard, Richard H. van Jaarsveld, Lesley Ades, Benjamin Cogne, Cyril Mignot, Wallid Deb, Marjolijn C. J. Jongmans, F. Sessions Cole, Marie-Jose H. van den Boogaard, Jennifer A. Wambach, Daniel J. Wegner, Sandra Yang, Vickie Hannig, Jennifer Ann Brault, Neda Zadeh, Bruce Bennetts, Boris Keren, Anne-Claire Gelineau, Zoee Powis, Meghan Towne, Kristine Bachman, Andrea Seeley, Anita E. Beck, Jennifer Morrison, Rachel Westman, Kelly Averill, Theresa Brunet, Judith Haasters, Melissa T. Carter, Matthew Osmond, Patricia G. Wheeler, Francesca Forzano, Shehla Mohammed, Yannis Trakadis, Andrea Accogli, Rachel Harrison, Yiran Guo, Hakon Hakonarson, Sophie Rondeau, Genevieve Baujat, Giulia Barcia, Rene Guenther Feichtinger, Johannes Adalbert Mayr, Martin Preisel, Frederic Laumonnier, Tilmann Kallinich, Alexej Knaus, Bertrand Isidor, Peter Krawitz, Uwe Voelker, Elke Hammer, Arnaud Droit, Evan E. Eichler, Ype Elgersma, Peter W. Hildebrand, Francois Bolduc, Elke Krueger, Stephane Bezieau
Summary: PSMC3 variants disrupt proteasome function and cause proteotoxic stress, leading to neurodevelopmental delay and intellectual disability.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Nuria Tubio-Santamaria, Ashok Kumar Jayavelu, Tina M. Schnoeder, Theresa Eifert, Chen-Jen Hsu, Florian Perner, Qirui Zhang, Daniela V. Wenge, Fynn M. Hansen, Joanna M. Kirkpatrick, Nidhi Jyotsana, Steven W. Lane, Bjoern von Eyss, Aniruddha J. Deshpande, Michael W. M. Kuehn, Juerg Schwaller, Clemens Cammann, Ulrike Seifert, Frederic Ebstein, Elke Krueger, Andreas Hochhaus, Michael Heuser, Alessandro Ori, Matthias Mann, Scott A. Armstrong, Florian H. Heidel
Summary: Targeting the immunoproteasome and Menin inhibitors can be a novel approach for the treatment of KMT2A-rearranged acute myeloid leukemia (AML).
Proceedings Paper
Computer Science, Interdisciplinary Applications
Dagmar Waltemath, Hilke Beelich, Philipp Toepfer, Corinna Bergelt, Agnes Floeel, Elpiniki Katsari, Elke Krueger, Stine Lutze, Michael Schoener, Sebastian Paschen, Moritz Roloff, Hanne Roth, Sylvia Stracke
Summary: Sex- and gender-related aspects play a vital role in medicine and biomedical research. Ignoring these aspects can result in lower quality research data and decreased generalizability of study results. To address this issue, we implemented a pilot program focused on gender awareness in a German medical faculty. The program aims to promote gender equality in clinical practice and research, and encourage gender-related clinical studies.
CARING IS SHARING-EXPLOITING THE VALUE IN DATA FOR HEALTH AND INNOVATION-PROCEEDINGS OF MIE 2023
(2023)