Article
Cell Biology
Qin Feng, Wenkai Xia, Zhong Feng, Yujun Tan, Yongxia Zhang, Deshan Liu, Guimin Zhang
Summary: The mechanism of accelerated aging in thyrotoxicosis mice was investigated in this study. Excess thyroxine led to cardiac hypertrophy, decreased hepatic synthetic capacity, and decreased hepatic and renal metabolic capacity. The main cause of organ senescence was identified as proteotoxicity, which resulted from intensified oxidative phosphorylation, excessive ribosome production, and impaired splicing and ubiquitin proteasome system function. This research provides a convenient and suitable animal model for studying aging mechanisms and antiaging drugs.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nobuyuki Tanahashi, Moeko Komiyama, Mina Tanaka, Yuta Yokobori, Shigeo Murata, Keiji Tanaka
Summary: This study reveals the regulatory mechanisms of proteasome activity in response to the nutritional state and identifies the important role of assembly protein Ump1 during this regulation.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2022)
Article
Cardiac & Cardiovascular Systems
Liuqing Yang, Nirmal Parajuli, Penglong Wu, Jinbao Liu, Xuejun Wang
Summary: The study establishes that PKA activates 26S proteasomes through pS14-Rpn6 and identifies pS14-Rpn6 as a key factor in cardiac proteinopathy.
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Abramo J. Manfredonia, Daniel A. Kraut
Summary: The ubiquitin-proteasome system is responsible for protein degradation in eukaryotic cells. The study showed that degradation of ubiquitin-independent degrons (UbIDs) is slower and relies on loosely folded substrates. Furthermore, UbID degradation is ATP-independent.
Article
Oncology
Mayra Tardelli de Jesus Testa, Paola Sanches Cella, Poliana Camila Marinello, Fernando Tadeu Trevisan Frajacomo, Camila de Souza Padilha, Patricia Chimin Perandini, Felipe Arruda Moura, Jose Alberto Duarte, Rubens Cecchini, Flavia Alessandra Guarnier, Rafael Deminice
Summary: This study aims to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice. The results suggest that resistance training can prevent excessive activation of STAT3 and the increased expression of key genes and proteins in the ubiquitin-proteasome and autophagy pathways.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wenyan Yang, Shiqun Wang, Shengqiang Tong, Wei-Dong Zhang, Jiang-Jiang Qin
Summary: This article provides an overview of the ubiquitin-proteasome system (UPS) and its role in pancreatic cancer. Studies indicate that mutations or aberrant expression of UPS members can lead to rewriting of the ubiquitination code, affecting tumor growth, metastasis, immune evasion, and drug resistance. The article also reviews current UPS modulators and analyzes their potential as cancer therapies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Chemistry, Physical
Lucas W. Henderson, Edie M. Sharon, Amit K. S. Gautam, Adam J. Anthony, Martin F. Jarrold, David H. Russell, Andreas Matouschek, David E. Clemmer
Summary: Mass spectrometry studies show that the stability of S. cerevisiae 20S proteasome undergoes related configurations and transitions during temperature changes, possibly linked to the opening of the proteolytic core. The study indicates that the proteasome remains intact and all transitions are reversible. Three types of structures are identified based on thermodynamic analysis: energetically stabilized closed configurations, high-entropy precursor states, and open pore structures. Opening of the 20S pore in the absence of the regulatory unit involves a charge-priming process. However, only a small fraction of precursor configurations actually open to expose the catalytic cavity.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Oncology
Tianchang Tao, Ningda Xu, Jiarui Li, Mingwei Zhao, Xiaoxin Li, Lvzhen Huang
Summary: Studies have found a correlation between the ubiquitin-proteasome system (UPS) and age-related macular degeneration (AMD). By knocking out the Ube3d gene in the retinal pigment epithelium (RPE) of mice, researchers observed retinal degeneration, vascular system attenuation, and decline in photoreceptor function. The RPE-specific Ube3d knockout mice also showed morphological changes similar to human AMD, suggesting a role of UPS dysfunction in the pathology of AMD. The loss of Ube3d also resulted in aberrant molecular characterizations associated with autophagy-lysosomal pathway, oxidative stress damage, and cell-cycle regulation.
JOURNAL OF PATHOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Alexei F. Kisselev
Summary: Proteasome is a crucial protein degradation machine in maintaining protein homeostasis and regulating cell functions. FDA-approved proteasome inhibitors are used for multiple myeloma treatment. Various inhibitors target different active sites of the proteasome, impacting its biological functions and identifying potential drug targets for disease treatment.
Article
Cell Biology
Zhiping Mi, Steven H. Graham
Summary: This review focuses on the potential role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury and recovery. It discusses the normal physiological functions of UCHL1, the effects of posttranslational modification sites and splice variants on UCHL1 function, mouse models with UCHL1 mutations and deletions, and the hypothesized role and pathogenic mechanisms of UCHL1 in neurodegenerative diseases and brain injury.
AGEING RESEARCH REVIEWS
(2023)
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
Physiology
Willem J. J. De Lange, Emily T. T. Farrell, Jonathan J. J. Hernandez, Alana Stempien, Caroline R. R. Kreitzer, Derek R. R. Jacobs, Dominique L. L. Petty, Richard L. L. Moss, Wendy C. C. Crone, J. Carter Ralphe
Summary: Truncation mutations in the cardiac myosin binding protein C (cMyBP-C) can cause hypertrophic cardiomyopathy (HCM). Using CRISPR-Cas9 technology, frame-shift mutations were introduced into MYBPC3 in human iPSCs to create heterozygous (cMyBP-C+/-) and homozygous (cMyBP-C-/-) mutant lines. Functional analysis of cardiomyocytes derived from these lines showed progressive contractile dysfunction and Ca2+-handling abnormalities in cMyBP-C-/- ECTs. RNA-seq analysis revealed differential expression of genes related to hypertrophy, sarcomeric function, Ca2+-handling, and metabolism in cMyBP-C+/- and cMyBP-C-/- ECTs.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Neurosciences
Zhiping Mi, Hao Liu, Marie E. Rose, Xiecheng Ma, Daniel P. Reay, Jie Ma, Jeremy Henchir, C. Edward Dixon, Steven H. Graham
Summary: UCHL1 is a multifunctional protein expressed at high levels in neurons throughout the brain, with its hydrolase activity playing a crucial role in the recovery after neuronal injury and the pathogenesis of neurodegenerative diseases.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Cell Biology
Gun West, Minttu Turunen, Anna Aalto, Laura Virtanen, Song-Ping Li, Tiina Helio, Annika Meinander, Pekka Taimen
Summary: This study reveals the intricate interplay between mutant lamins A and C and the protein degradation machinery. Mutant lamins A and C reduce the activity of the ubiquitin-proteasome system (UPS), leading to accumulation of K48-ubiquitin chains. However, compensatory enhanced autophagy can degrade the mutant lamins A and C. Furthermore, pharmacological interventions that enhance protein degradation can be beneficial for maintaining cellular homeostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(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)
Article
Multidisciplinary Sciences
Gabriella Captur, Carolyn Y. Ho, Saskia Schlossarek, Janet Kerwin, Mariana Mirabel, Robert Wilson, Stefania Rosmini, Chinwe Obianyo, Patricia Reant, Paul Bassett, Andrew C. Cook, Susan Lindsay, William J. McKenna, Kevin Mills, Perry M. Elliott, Timothy J. Mohun, Lucie Carrier, James C. Moon
SCIENTIFIC REPORTS
(2016)
Article
Physiology
Nicoletta Piroddi, E. Rosalie Witjas-Paalberends, Claudia Ferrara, Cecilia Ferrantini, Giulia Vitale, Beatrice Scellini, Paul J. M. Wijnker, Vasco Sequiera, Dennis Dooijes, Cristobal dos Remedios, Saskia Schlossarek, Man Ching Leung, Andrew Messer, Douglas G. Ward, Annibale Biggeri, Chiara Tesi, Lucie Carrier, Charles S. Redwood, Steven B. Marston, Jolanda van der Velden, Corrado Poggesi
JOURNAL OF GENERAL PHYSIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Antonia T. L. Zech, Sonia R. Singh, Saskia Schlossarek, Lucie Carrier
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2020)
Article
Cardiac & Cardiovascular Systems
Karoline Morhenn, Thomas Quentin, Helen Wichmann, Michael Steinmetz, Maksymilian Prondzynski, Klaus-Dieter Soehren, Torsten Christ, Birgit Geertz, Sabine Schroeder, Friedrich A. Schoendube, Gerd Hasenfuss, Saskia Schlossarek, Wolfram H. Zimmermann, Lucie Carrier, Thomas Eschenhagen, Jean-Rene Cardinaux, Susanne Lutz, Elke Oetjen
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2019)
Article
Anatomy & Morphology
Patricia Garcia-Canadilla, Andrew C. Cook, Timothy J. Mohun, Onyedikachi Oji, Saskia Schlossarek, Lucie Carrier, William J. McKenna, James C. Moon, Gabriella Captur
JOURNAL OF ANATOMY
(2019)
Article
Medicine, Research & Experimental
Maksymilian Prondzynski, Marc D. Lemoine, Antonia T. L. Zech, Andras Horvath, Vittoria Di Mauro, Jussi T. Koivumaki, Nico Kresin, Josefine Busch, Tobias Krause, Elisabeth Kraemer, Saskia Schlossarek, Michael Spohn, Felix W. Friedrich, Julia Muench, Sandra D. Laufer, Charles Redwood, Alexander E. Volk, Arne Hansen, Giulia Mearini, Daniele Catalucci, Christian Meyer, Torsten Christ, Monica Patten, Thomas Eschenhagen, Lucie Carrier
EMBO MOLECULAR MEDICINE
(2019)
Article
Multidisciplinary Sciences
Alexander Dutsch, Paul J. M. Wijnker, Saskia Schlossarek, Felix W. Friedrich, Elisabeth Kraemer, Ingke Braren, Marc N. Hirt, David Breniere-Letuffe, Alexandra Rhoden, Ingra Mannhardt, Thomas Eschenhagen, Lucie Carrier, Giulia Mearini
SCIENTIFIC REPORTS
(2019)
Article
Cardiac & Cardiovascular Systems
Christina Yingxian Chen, Alexander K. Salomon, Matthew A. Caporizzo, Sam Curry, Neil A. Kelly, Kenneth Bedi, Alexey Bogush, Elisabeth Kramer, Saskia Schlossarek, Philip Janiak, Marie-Jo Moutin, Lucie Carrier, Kenneth B. Margulies, Benjamin L. Prosser
CIRCULATION RESEARCH
(2020)
Article
Cell Biology
Sonia R. Singh, Moritz Meyer-Jens, Erda Alizoti, W. Clark Bacon, Gregory Davis, Hanna Osinska, James Gulick, Silke Reischmann-Duesener, Ellen Orthey, Patrick M. McLendon, Jeffery D. Molkentin, Saskia Schlossarek, Jeffrey Robbins, Lucie Carrier
Summary: The study revealed that ZNF418 activates the ALP, inhibits the UPS, and regulates genes associated with cardiomyocyte structure and function. RNA-seq analysis showed that ZNF418 also plays a role in regulating genes involved in cardiac development and/or hypertrophy.
Article
Cardiac & Cardiovascular Systems
Maike Schuldt, Jiayi Pei, Magdalena Harakalova, Larissa M. Dorsch, Saskia Schlossarek, Michal Mokry, Jaco C. Knol, Thang Pham, Tim Schelfhorst, Sander R. Piersma, Cris Dos Remedios, Michiel Dalinghaus, Michelle Michels, Folkert W. Asselbergs, Marie-Jo Moutin, Lucie Carrier, Connie R. Jimenez, Jolanda van der Velden, Diederik W. D. Kuster
Summary: The study found that microtubules and their detyrosination play an important role in the pathomechanism of patients with HCMSMP, potentially serving as a target for improving cardiac function. However, the beneficial effect may be limited in patients with HCMSMN.
CIRCULATION-HEART FAILURE
(2021)
Article
Physiology
Kristin Wenzel, Elisabeth Kraemer, Birgit Geertz, Lucie Carrier, Stephan B. Felix, Stephanie Koenemann, Saskia Schlossarek
Summary: In a mouse model of eccentric left ventricular hypertrophy, alterations were observed in both the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP), with a repression of the ALP during the initiation process, but an induction of the ALP at the level of autophagosome-lysosome fusion and the delivery of ubiquitinated cargo to the ALP for degradation.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Konstantina Stathopoulou, Josef Schnittger, Janice Raabe, Frederic Fleischer, Nils Mangels, Angelika Piasecki, Jane Findlay, Kristin Hartmann, Susanne Krasemann, Saskia Schlossarek, June Uebeler, Viktor Wixler, Derek J. Blake, George S. Baillie, Lucie Carrier, Elisabeth Ehler, Friederike Cuello
Summary: This study identifies a direct interaction between FHL2 and CMYA5 in cardiac myocytes, which may impact the subcellular compartmentation of CMYA5.
Correction
Medicine, Research & Experimental
Maksymilian Prondzynski, Marc D. Lemoine, Antonia T. L. Zech, Andras Horvath, Vittoria Di Mauro, Jussi T. Koivumaki, Nico Kresin, Josefine Busch, Tobias Krause, Elisabeth Kramer, Saskia Schlossarek, Michael Spohn, Felix W. Friedrich, Julia Muench, Sandra D. Laufer, Charles Redwood, Alexander E. Volk, Arne Hansen, Giulia Mearini, Daniele Catalucci, Christian Meyer, Torsten Christ, Monica Patten, Thomas Eschenhagen, Lucie Carrier
EMBO MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Antonia T. L. Zech, Maksymilian Prondzynski, Sonia R. Singh, Niels Pietsch, Ellen Orthey, Erda Alizoti, Josefine Busch, Alexandra Madsen, Charlotta S. Behrens, Moritz Meyer-Jens, Giulia Mearini, Marc D. Lemoine, Elisabeth Kraemer, Diogo Mosqueira, Sanamjeet Virdi, Daniela Indenbirken, Maren Depke, Manuela Gesell Salazar, Uwe Voelker, Ingke Braren, William T. Pu, Thomas Eschenhagen, Elke Hammer, Saskia Schlossarek, Lucie Carrier
Summary: This study evaluated the impact of ACTN2 gene variants on cardiomyocyte structure and function. The results showed that the variants led to abnormal cellular phenotypes, including multinucleation, protein aggregation, hypertrophy, and myofibrillar disarray. Additionally, the variants activated proteolytic systems and impaired cardiac force. This study highlights the cellular pathology caused by ACTN2 gene variants and its importance in understanding ACTN2-associated cardiomyopathies.
Article
Cardiac & Cardiovascular Systems
Sonia R. Singh, Antonia T. L. Zech, Birgit Geertz, Silke Reischmann-Duesener, Hanna Osinska, Maksymilian Prondzynski, Elisabeth Kraemer, Qinghang Meng, Charles Redwood, Jolanda van der Velden, Jeffrey Robbins, Saskia Schlossarek, Lucie Carrier
CIRCULATION-HEART FAILURE
(2017)