Article
Medicine, Research & Experimental
Goekhan Guener, Marlene Assfalg, Kai Zhao, Tobias Dreyer, Shibojyoti Lahiri, Yun Lo, Bianca Ionela Slivinschi, Axel Imhof, Georg Jocher, Laura Strohm, Christian Behrends, Dieter Langosch, Holger Bronger, Christopher Nimsky, Joerg W. Bartsch, Stanley R. Riddell, Harald Steiner, Stefan F. Lichtenthaler
Summary: Fn14 is cleaved by the protease gamma-secretase, leading to secretion of sFn14. Inhibition of gamma-secretase increases full-length Fn14 at the cell surface and enhances TWEAK ligand-stimulated Fn14 signaling. The release of sFn14 can be detected in tumor cells, plasma, and blood from cancer patients, suggesting it as a biomarker for monitoring gamma-secretase activity.
EMBO MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Laura Hobohm, Tomas Koudelka, Fenja H. Bahr, Jule Truberg, Sebastian Kapell, Sarah-Sophie Schacht, Daniel Meisinger, Marion Mengel, Alexander Jochimsen, Anna Hofmann, Lukas Heintz, Andreas Tholey, Matthias Voss
Summary: This study identifies more than 20 substrates of the intramembrane protease SPPL3 and demonstrates its significant role in Golgi enzyme turnover, secretion, and regulation of global glycosylation pathways.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Torben Mentrup, Florencia Cabrera-Cabrera, Bernd Schroeder
Summary: The LOX-1 receptor plays a crucial role in atherosclerosis, promoting oxLDL uptake and signaling cascade leading to foam cell formation. Proteolysis acts as a regulatory mechanism for LOX-1 function, generating cleavage products with different biological functions and potential diagnostic value.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Environmental Sciences
Tsan-Hung Chiu, Chang-Wen Ku, Tsung-Jung Ho, Kun-Ling Tsai, Yi-Dung Yang, Hsiu-Chung Ou, Hsiu- Chen
Summary: Atherosclerotic lesions are a leading cause of cardiovascular diseases. Oxidized low-density lipoprotein (OxLDL) is a crucial risk factor for atherosclerosis as it contributes to endothelial dysfunction and foam cell formation. This study explores the potential protective effects of Schisanhenol, a compound extracted from the fruit of Schisandra rubriflora, against OxLDL-mediated endothelial damage. Results show that Schisanhenol reduces the expression of lectin-like OxLDL receptor-1 (LOX-1) and prevents detrimental effects induced by OxLDL, such as downregulation of endothelial nitric oxide synthase (eNOS) and activation of inducible NOS (iNOS) and inflammatory responses.
ENVIRONMENTAL TOXICOLOGY
(2023)
Review
Biophysics
David Sprinzak, Stephen C. Blacklow
Summary: Notch signaling is a conserved system that influences cell fate decisions in the development of multicellular organisms. NICD plays a key role in this pathway by regulating gene expression. The article reviews the molecular basis of Notch signal transduction and its implications in different cellular contexts.
ANNUAL REVIEW OF BIOPHYSICS, VOL 50, 2021
(2021)
Article
Biology
Sandra Olenic, Lim Heo, Michael Feig, Lee Kroos
Summary: This study reveals a novel mechanism of inhibition for intramembrane proteases, which has implications for relief from inhibition in vivo and the design of potential therapeutic inhibitors.
Article
Biology
Lukas P. Feilen, Shu-Yu Chen, Akio Fukumori, Regina Feederle, Martin Zacharias, Harald Steiner
Summary: The activity of intramembrane proteases is modulated by lipid bilayers, and this study reveals the mechanism linking lipid environment to structural dynamics. The lipid bilayer plays a critical role in stabilizing the structure and arranging the active site of intramembrane protease.
Article
Medicine, Research & Experimental
Chao Tang, Ximei Wu, Qianlei Ren, Minli Yao, Shouying Xu, Ziyi Yan
Summary: This study uncovers a novel mechanism controlling Hh signaling through the activation of Rac1 and subsequent translocation of Gli. Rac1 activation affects KIF3A phosphorylation and IFT88 stability, thereby disrupting SuFu-Gli complex formation and releasing Gli for nuclear translocation.
Article
Plant Sciences
Xiaohui Su, Bei Yuan, Xueying Tao, Wanyi Guo, Xia Mao, Anguo Wu, Qian Wang, Chunfang Liu, Yanqiong Zhang, Xiangying Kong, Lan Han, Na Lin
Summary: In this study, the Chinese patent medicine Yuxuebi was found to have anti-angiogenic effects in collagen-induced arthritis and VEGF-induced HUVECs. Yuxuebi reduced disease severity and ameliorated pathological features in arthritis models, suppressed angiogenesis, and inhibited the LOX/Ras/Raf-1 signaling pathway. These findings suggest that Yuxuebi may be a potential therapeutic option for rheumatoid arthritis.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Shristi Pawnikar, Brenda S. Magenheimer, Ericka Nevarez Munoz, Robin L. Maser, Yinglong Miao
Summary: This study combines experimental and computational methods to elucidate the activation mechanism of Polycystin-1 (PC1), which is crucial for future drug design targeting PC1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Shristi Pawnikar, Brenda S. Magenheimer, Ericka Nevarez Munoz, Robin L. Maser, Yinglong Miao
Summary: PC1 is a GPCR that plays a crucial role in ADPKD, and its activation mechanism is still unclear. This study suggests that the activation of PC1 by its tethered agonist (TA) may involve residue interactions between the stalk, TOP domain, and putative pore loop. These findings provide insights for future drug design targeting PC1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Gargi Roy, Anush Chakraborty, Bharati Swami, Lalit Pal, Charvi Ahuja, Soumen Basak, Sangeeta Bhaskar
Summary: The study reveals that MIP immunotherapy activates type 1 interferon signaling pathway to induce antitumor responses. Additionally, MIP reduces the migration of Tregs into the tumor microenvironment and enhances the activation of immunosuppressive tumor resident DCs, which in turn promotes the proliferation and effector function of CD8+ T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Anjali Pande, Bong-Gyu Mun, Murtaza Khan, Waqas Rahim, Da-Sol Lee, Geun-Mo Lee, Tiba Nazar Ibrahim Al Azawi, Adil Hussain, Byung-Wook Yun
Summary: The versatility of nitric oxide as a signaling molecule in plant biology involves post-translational modifications of target proteins and their subsequent proteasomal degradation through ubiquitylation. The close link between NO-mediated PTMs and ubiquitylation highlights the intricate mechanisms of NO signal perception and transduction. This review provides insights into the pathways connecting NO-PTMs with ubiquitylation, shedding light on the regulation of protein degradation and activity in plants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Milena Jovanovic, Gali Guterman-Ram, Joan C. Marini
Summary: Osteogenesis imperfecta (OI) is a diverse genetic and phenotypic skeletal disorder characterized by bone fragility, growth deficiency, and skeletal deformity. Research focuses on defects in collagen, abnormal bone mineralization, different inheritance patterns, and various genetic mutations related to OI.
Article
Biochemistry & Molecular Biology
Anja C. Nagel, Dominik Mueller, Mirjam Zimmermann, Anette Preiss
Summary: The membrane-bound Notch regulator (Mnr) supports Notch signaling by promoting the cleavage of the Notch receptor, which in turn enhances Notch receptor activation. Overexpression of Mnr stimulates γ-secretase activity, while knockdown of Mnr inhibits this activity, demonstrating Mnr as a positive regulator of Notch signaling.
Article
Biochemistry & Molecular Biology
Christian Treitz, Juliane Gottwald, Eva Gericke, Peter Urban, Rolf Ruediger Meliss, Hans-Detlef Axmann, Frank Siebert, Karsten Becker, Andreas Tholey, Christoph Roecken
Summary: Amyloidosis is a disease group characterized by pathological aggregation and deposition of peptides in tissues, with the study finding 83 proteins specifically enriched in ATTR amyloid, including 22 members of the complement system associated with the disease. These data support the hypothesis that the complement system is activated in ATTR amyloidosis.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2022)
Article
Chemistry, Analytical
Philipp T. Kaulich, Liam Cassidy, Konrad Winkels, Andreas Tholey
Summary: In top-down proteomics, pre-fractionation is crucial for high confidence identification of proteoforms and increased proteome coverage. The use of field asymmetric ion mobility spectrometry (FAIMS) has shown to be beneficial, but only external compensation voltage (CV) stepping has been demonstrated. This study investigated the use of internal CV stepping for single-shot TD analysis and optimized MS parameters for different CVs. The optimized multi-CV method significantly increased the number of identified protein groups and proteoforms without increasing measurement time.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tomas Koudelka, Konrad Winkels, Patrick Kaleja, Andreas Tholey
Summary: Proteases were found to hydrolyze peptide bonds specifically, modulating the fate and activity of proteins in various biological processes. N- and C-terminomics play crucial roles in identifying protease substrates and their functions. Different strategies and workflows have been developed to increase sensitivity, coverage depth, and throughput in proteomics research.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Lukas Seebauer, Yanni Schneider, Alice Drobny, Sonja Ploetz, Tomas Koudelka, Andreas Tholey, Iryna Prots, Beate Winner, Friederike Zunke, Juergen Winkler, Wei Xiang
Summary: In this study, the impact of aSyn on microtubule organization was investigated in cell models and patient-derived neurons. The results suggest that aSyn aggregation interferes with microtubule organization, leading to impaired neuritic phenotypes in Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Torben Mentrup, Anna Yamina Stumpff-Niggemann, Nadja Leinung, Christine Schlosser, Katja Schubert, Rebekka Wehner, Antje Tunger, Valentin Schatz, Patrick Neubert, Ann-Christine Gradtke, Janina Wolf, Stefan Rose-John, Paul Saftig, Alexander Dalpke, Jonathan Jantsch, Marc Schmitz, Regina Fluhrer, Ilse D. Jacobsen, Bernd Schroeder
Summary: Dectin-1 plays a critical role in recognizing fungal pathogens through pattern recognition receptors on immune cells. Activation of Dectin-1a results in the formation of a stable receptor fragment lacking the ligand binding domain, which contributes to signal transduction in phagosomal membranes and is terminated by intramembrane proteases SPPL2a and 2b.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ludwig Werny, Antonia Grogro, Kira Bickenbach, Cynthia Bulck, Fred Armbrust, Tomas Koudelka, Kriti Pathak, Franka Scharfenberg, Martin Sammel, Farah Sheikhouny, Andreas Tholey, Stefan Linder, Christoph Becker-Pauly
Summary: This study investigated the interaction between membrane-type-I matrix metalloproteinase (MT1-MMP) and meprin beta, revealing a potential regulatory connection between the two enzymes.
Article
Multidisciplinary Sciences
Amanda Heard, Jack H. Landmann, Ava R. Hansen, Alkmini Papadopolou, Yu-Sung Hsu, Mehmet Emrah Selli, John M. Warrington, John Lattin, Jufang Chang, Helen Ha, Martina Haug-Kroeper, Balraj Doray, Saar Gill, Marco Ruella, Katharina E. Hayer, Matthew D. Weitzman, Abby M. Green, Regina Fluhrer, Nathan Singh
Summary: Loss of surface CD19 expression by leukemic cells leads to resistance and relapse to CD19-targeted CAR-T therapies. Hyperglycosylation of CD19 due to the loss of SPPL3 in malignant B cells inhibits CAR T cell effector function and suppresses anti-tumor cytotoxicity. This study reveals post-translational modification of CD19 as a mechanism of antigen escape from CAR T cell therapy.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Liam Cassidy, Philipp T. Kaulich, Andreas Tholey
Summary: Microproteins and SEPs can undergo various posttranslational modifications like other proteins. However, traditional proteomic methods face challenges in identifying, quantifying and characterizing proteoforms. Top-down proteomics, in contrast, allows for direct identification of intact proteoforms. This article provides an overview of modified microproteins and SEPs, introduces proteoform terminology, and compares the advantages and disadvantages of traditional bottom-up and top-down proteomic workflows. It also discusses future developments in top-down proteomics for proteoform-centric analysis of microproteins and SEPs.
Article
Chemistry, Multidisciplinary
Jan Leipert, Philipp T. Kaulich, Max K. Steinbach, Britta Steer, Konrad Winkels, Christine Blurton, Matthias Leippe, Andreas Tholey
Summary: Researchers have developed a sample preparation method based on protein aggregation and acidic elution, allowing for sensitive protein identification analysis of single nematodes on a digital microfluidics device. Compared to in-tube sample preparation, this method increases proteoform identifications by 46%. Label-free quantification also reveals changes in proteoform abundance that cannot be distinguished by bottom-up proteomics. This workflow facilitates proteoform-focused analysis on limited availability samples.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Johanna Rueter, Gerald Rimbach, Christian Treitz, Anke Schloesser, Kai Lueersen, Andreas Tholey, Patricia Huebbe
Summary: The study identified protein-protein interactions of APOE with BCKDHA and VDAC1, suggesting a possible involvement of APOE in mitochondrial processes and adaptation to hepatic energy demands. The activity of the BCKD enzyme complex was higher in obese APOE4 mice, while the interaction with VDAC1 was induced upon dietary restriction.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemical Research Methods
Philipp T. Kaulich, Liam Cassidy, Andreas Tholey
Summary: Efficient proteoform separation is crucial for top-down (TD) proteomics. A two-dimensional low pH/low pH reversed-phase liquid chromatography separation scheme was developed. The optimized separation scheme led to the identification of more than 4900 proteoforms from 1250 protein groups in Caco-2 cells. The low/low pH separation strategy resulted in a higher number of proteoform identifications below 20 kDa compared to the previously published high pH/low pH strategy.
Article
Biochemical Research Methods
Ayako Takemori, Philipp T. Kaulich, Ryo Konno, Yusuke Kawashima, Yuto Hamazaki, Ayuko Hoshino, Andreas Tholey, Nobuaki Takemori
Summary: Middle-down proteomics (MDP) is an analytical method that uses proteases to generate large peptides for mass spectrometry analysis. It is particularly useful for studying high-molecular-weight proteins. In this study, we applied a multidimensional separation workflow combining gel-based prefractionation with LC-FAIMS MS for deep MDP. By improving the digestion conditions and implementing size fractionation and additional ion mobility fractionation, we were able to increase the detectable peptide length and explore proteoform information not covered by conventional top-down proteomics.
Article
Microbiology
Jerome Genth, Kathrin Schaefer, Liam Cassidy, Simon Graspeuntner, Jan Rupp, Andreas Tholey
Summary: Short open reading frames (sORFs) can encode small proteins called sORF-encoded peptides (SEP) that play important roles in various physiological processes. Using proteomics techniques, researchers identified 45 novel and previously reported SEPs in single cultures of Blautia producta under different growth conditions and stress exposure. The results suggest that the biosynthesis of specific SEPs is not limited to bacterial interactions within the microbiome but is influenced by growth and environmental conditions during cultivation.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemical Research Methods
Kyowon Jeong, Philipp T. Kaulich, Wonhyeuk Jung, Jihyung Kim, Andreas Tholey, Oliver Kohlbacher
Summary: Top-down proteomics provides more comprehensive proteoform-level information, but reliable data analysis remains challenging. The conventional FDR estimation method may not work at the proteoform level, and the precursor deconvolution error rate should be taken into account.
Meeting Abstract
Oncology
C. Buehring-Uhle, P. Smit, A. Negraschus, V. Morath, U. Goldmann, A. Papadopoulou, M. Heider, J. Riviere, K. Goetze, L. Heinz, R. Fluhrer, M. Moser, G. Superti-Furga, F. Bassermann, R. Eichner
ONCOLOGY RESEARCH AND TREATMENT
(2022)