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
Oncology
Gregoire Quinet, Wendy Xolalpa, Diana Reyes-Garau, Nuria Profitos-Peleja, Mikel Azkargorta, Laurie Ceccato, Maria Gonzalez-Santamarta, Maria Marsal, Jordi Andilla, Fabienne Aillet, Francesc Bosch, Felix Elortza, Pablo Loza-Alvarez, Brigitte Sola, Olivier Coux, Rune Matthiesen, Gael Roue, Manuel S. Rodriguez
Summary: The research identified an enrichment of autophagy-lysosome system (ALS) components in bortezomib (BTZ)-resistant cells in mantle cell lymphoma (MCL) patients. By blocking proteaphagy, the normal proteasomal activity was reactivated and the BTZ antitumor effect was restored in vitro and in vivo models of BTZ resistance. These findings suggest a proteolytic switch from the ubiquitin-proteasome system (UPS) to ALS in B-cell lymphoma refractory to proteasome inhibition, opening up new therapeutic avenues for treatment-resistant tumors.
Review
Oncology
Yonggang Pei, Erle S. Robertson
Summary: This review discusses the interaction between Epstein-Barr virus (EBV) and the ubiquitin-proteasome system, as well as their importance in EBV-mediated oncogenesis. Deregulation of the ubiquitin-proteasome system plays a critical role in many human cancers, and EBV manipulates this system to induce tumor formation. Recent studies further enhance our understanding of the ubiquitin-proteasome system in EBV infection and provide new strategies for the treatment of EBV-associated cancers.
Article
Pharmacology & Pharmacy
Narathip Naradun, Krajang Talabnin, Kanyavee Issarangkul Na Ayuttha, Chutima Talabnin
Summary: Cholangiocarcinoma is a lethal malignancy with limited treatment options. Piperlongumine, a biologically active alkaloid, has shown potential as a therapeutic option for cholangiocarcinoma by inducing cancer cell death. Combination treatment with piperlongumine and a proteasome inhibitor further enhances the anti-cancer activity. This research provides valuable insights into the potential use of piperlongumine as an alternative therapy for cholangiocarcinoma.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Da-cai Xu, Li Yang, Pei-quan Zhang, Ding Yan, Qian Xue, Qing-tian Huang, Xiao-fen Li, Ya-li Hao, Dao-lin Tang, Q. Ping Dou, Xin Chen, Jin-bao Liu
Summary: The study synthesized a novel gold (I) complex named Na-AuPT that exhibited high water solubility and potent inhibitory effects on the growth of multiple cancer cell lines, as well as induction of apoptosis. In nude mice bearing xenografts, Na-AuPT administration significantly inhibited tumor growth and induced cell death of primary mononuclear cells from patients with acute myeloid leukemia, suggesting its potential as a promising metal-based proteasome inhibitor for cancer therapy.
ACTA PHARMACOLOGICA SINICA
(2022)
Review
Oncology
Azmi Yerlikaya, Ertan Kanbur, Bruce A. Stanley, Emrah Tumer
Summary: The ubiquitin-proteasome pathway is involved in almost all cellular processes and recent studies indicate that epigenetic changes are also regulated by this pathway. Alterations in the regulation of the ubiquitin-proteasome pathway have been discovered in many pathological conditions, and the interaction between the ubiquitin-proteasome and epigenetic pathways may offer new treatment strategies for cancer.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Tanya R. Porras-Yakushi, Justin M. Reitsma, Michael J. Sweredoski, Raymond J. Deshaies, Sonja Hess
Summary: The study conducted a large-scale ubiquitylome analysis of proteasome inhibitors and identified numerous unique ubiquitylation sites in protein groups. It also highlighted candidate proteins for further study, indicating potential targets for the ubiquitin proteasome system. Additionally, the research observed a decrease in ubiquitylation of the tumor suppressor protein MORF4L1 upon proteasome inhibition, suggesting a potential anti-tumor effect of certain proteasome inhibitors.
JOURNAL OF PROTEOMICS
(2021)
Article
Multidisciplinary Sciences
Afu Fu, Victoria Cohen-Kaplan, Noa Avni, Ido Livneh, Aaron Ciechanover
Summary: The degradation of proteins through the ubiquitin-proteasome system is a complex multistep process that relies on the coordinated activity of various enzymes. Nuclear condensates containing essential components like p62 play a crucial role in protein quality control and degradation, especially under stress conditions. These assemblies, generated through liquid-liquid phase separation, efficiently facilitate proteolysis of nuclear proteins and unassembled proteasome subunits, indicating their involvement in cellular protein quality control.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Gonca cetin, Sandro Klafack, Maja Studencka-Turski, Elke Kruger, Frederic Ebstein
Summary: The ubiquitin-proteasome system (UPS) is a crucial protein degradation system in cells, particularly impacting immune cells and their rapid functional remodeling during immune activation. Recent research has shed light on the molecular mechanisms by which UPS contributes to immune responses and its role in immune disorders like cancer and auto-inflammatory diseases.
Article
Virology
Martin Voss, Vera Braun, Clara Bredow, Peter-Michael Kloetzel, Antje Beling
Summary: Infection with coxsackievirus B3 results in impaired protein homeostasis and accumulation of ubiquitinylated proteins, attributed to viral proteins 2B and 3A. During the exponential replication phase, oxidative damage of membrane proteins is reduced due to the recruitment of glutathione. The proteasome is shown to play a role in processing viral precursor proteins during infection.
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)
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
Cell Biology
Jason Q. Tang, Mary M. Marchand, Gianluca Veggiani
Summary: Protein turnover, regulated by the ubiquitin-proteasome system (UPS), is important for cellular homeostasis. Dysregulation of the UPS is associated with diseases and UPS enzymes are attractive therapeutic targets. However, redundancies of UPS enzymes make it challenging to identify precise drug targets. Engineered ubiquitin has emerged as a promising alternative to guide the development of small molecules targeting novel surfaces.
Article
Biochemistry & Molecular Biology
Martyna Bednarczyk, Malgorzata Muc-Wierzgon, Sylwia Dziegielewska-Gesiak, Dariusz Waniczek
Summary: This study analyzed the changes in the transcriptional activity of autophagy-related genes and the ubiquitination process in colorectal cancer tissue. The results showed dysregulation of ubiquitination and autophagy processes, especially in the early stages of cancer, which may contribute to tumor progression and poor prognosis.
Letter
Food Science & Technology
Zdenek Dvorak
FOOD AND CHEMICAL TOXICOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Jan Vanco, Zdenek Travnicek, Radka Krikavova, Jana Galikova, Zdenek Dvorak, Marta Chalupova
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
(2017)
Article
Chemistry, Inorganic & Nuclear
Ali Osman S. Altoum, Jan Vanco, Radka Krikavova, Zdenek Travnicek, Zdenek Dvofak, Muhammad Altaf, Saeed Ahmad, Adam A. A. Sulaiman, Anvarhusein A. Isab
Article
Pharmacology & Pharmacy
Martina Stepankova, Barbora Pastorkova, Petr Bachleda, Zdenek Dvorak
Article
Toxicology
Radim Vrzal, Aneta Vrzalova, Aneta Grycova, Zdenek Dvorak
TOXICOLOGY LETTERS
(2017)
Meeting Abstract
Oncology
Martin Mistrik, Zdenek Skrott, Marian Hajduch, Soren Friis, Petr Dzubak, Jan Gursky, Dusana Majera, Tomas Ozdian, Jana Vaclavkova, Martina Michalova, Pavla Pouckova, Boris Cvek, Klaus Kaae Andersen, Jiri Bartek
Article
Multidisciplinary Sciences
Franziska Roth-Walter, Cornelia Bergmayr, Sarah Meitz, Stefan Buchleitner, Caroline Stremnitzer, Judit Fazekas, Anna Moskovskich, Mario A. Mueller, Georg A. Roth, Krisztina Manzano-Szalai, Zdenek Dvorak, Alina Neunkirchner, Erika Jensen-Jarolim
SCIENTIFIC REPORTS
(2017)
Article
Biochemistry & Molecular Biology
Barbora Vyhlidalova, Kristyna Krasulova, Petra Pecinkova, Adela Marcalikova, Radim Vrzal, Lenka Zemankova, Jan Vanco, Zdenek Travnicek, Jan Vondracek, Martina Karasova, Sridhar Mani, Zdenek Dvorak
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Jan Vanco, Zdenek Travnicek, Jan Hosek, Tomas Malina, Zdenek Dvorak
Summary: A series of new heteroleptic copper(II) complexes were prepared and showed effective antiproliferative activity against various human cancer cell lines, while exhibiting low toxicity on healthy human cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Aneta Vrzalova, Petra Pecinkova, Peter Illes, Sona Gurska, Petr Dzubak, Martin Szotkowski, Marian Hajduch, Sridhar Mani, Zdenek Dvorak
Summary: Aryl hydrocarbon receptor (AHR) plays important roles in intestinal physiology and is activated by microbial metabolites, with synergistic effects observed in combinations of low- or medium-efficacy agonists. High-efficacy agonists may show antagonist effects on AHR activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Martina Karasova, Jirina Prochazkova, Zuzana Tylichova, Radek Fedr, Miroslav Ciganek, Miroslav Machala, Zdenek Dvorak, Barbora Vyhlidalova, Iveta Zuvalova, Jiri Ehrmann, Jan Bouchal, Zdenek Andrysik, Jan Vondracek
Summary: Aryl hydrocarbon receptor (AhR) plays diverse physiological roles in cellular processes such as proliferation, migration, and immune response control. Studies suggest that AhR may contribute to the regulation of energy balance and cellular metabolism, particularly fatty acid synthesis. In colon tumor cells, disruption of AhR activity may limit proliferation and affect endogenous fatty acid metabolism.
Article
Pharmacology & Pharmacy
Zdenek Travnicek, Tomas Malina, Jan Vanco, Marek Sebela, Zdenek Dvorak
Summary: The paper describes the synthesis and characterization of six heteroleptic copper(II) complexes with different ligands. The results showed that complex 2 exhibited high cytotoxicity against cancer cells, while showing low toxicity against healthy cells. Further experiments revealed that complex 2 induced apoptosis and autophagy in A2780 cancer cells through the activation of caspases 3/7, ROS overproduction, and autophagy induction.
Article
Biochemistry & Molecular Biology
Andreas Regner, Nathalie Szepannek, Markus Wiederstein, Aila Fakhimahmadi, Luis F. F. Paciosis, Bart R. R. Blokhuis, Frank A. A. Redegeld, Gerlinde Hofstetter, Zdenek Dvorak, Erika Jensen-Jarolim, Karin Hufnagl, Franziska Roth-Walter
Summary: Bet v 1 is a major allergen in birch pollen, with up to 95% of birch-sensitized patients responding to it. It belongs to the pathogenesis-related PR 10 family and is involved in plant defense. This study found that Bet v 1 can bind to iron quercetin complexes (FeQ2), reducing allergenicity and contributing to anti-inflammatory stimuli in human monocytes.
Article
Biochemistry & Molecular Biology
Aila Fakhimahmadi, Ilir Hasanaj, Gerlinde Hofstetter, Clara Pogner, Markus Gorfer, Markus Wiederstein, Nathalie Szepannek, Rodolfo Bianchini, Zdenek Dvorak, Sebastian A. Jensen, Markus Berger, Erika Jensen-Jarolim, Karin Hufnagl, Franziska Roth-Walter
Summary: The major allergen Alt a 1 from Alternaria alternata is highly associated with severe allergic asthma. Alt a 1 can bind to micronutrients such as iron-quercetin complexes (FeQ2) and affect antigen presentation. It functions as an innate defense protein, binding strongly to FeQ2, and shows different enzymatic activity depending on its ligand-filled state. The uptake of Alt a 1 by cells alters cellular iron levels and can activate the Arylhydrocarbon receptor (AhR).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Radim Vrzal, Adela Marcalikova, Kristyna Krasulova, Lenka Zemankova, Zdenek Dvorak
Summary: Herbal extract jasmone exhibits potent antagonistic effects on the aryl hydrocarbon receptor (AhR) and has potential medical applications. It inhibits AhR activation by various substances and regulates downstream signaling events. This discovery is important for understanding the therapeutic potential of jasmone in AhR-related conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
