Article
Biochemical Research Methods
Bryan T. MacDonald, Hasmik Keshishian, Charles C. Mundorff, Alessandro Arduini, Daniel Lai, Kayla Bendinelli, Nicholas R. Popp, Bidur Bhandary, Karl R. Clauser, Harrison Specht, Nadine H. Elowe, Dylan Laprise, Yi Xing, Virendar K. Kaushik, Steven A. Carr, Patrick T. Ellinor
Summary: This study identified ADAMTS7 extracellular substrates and their cleavage sites using the TAILS method, providing potential candidates for exploring disease-related biological substrates and facilitating the development of ADAMTS7 biomarkers.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Biochemistry & Molecular Biology
Ahmad Aljohmani, Bastian Opitz, Markus Bischoff, Daniela Yildiz
Summary: This study found that infection with Pseudomonas aeruginosa and Streptococcus pneumoniae stimulates the activation of ADAM10 in epithelial cells, leading to inflammatory cell recruitment and loss of barrier integrity. The activation is based on the toxin repertoire rather than the bacterial particle itself.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Jennifer Vandooren, Rafaela Vaz Sousa Pereira, Estefania Ugarte-Berzal, Vasily Rybakin, Sam Noppen, Melissa R. Stas, Eline Bernaerts, Eva Ganseman, Mieke Metzemaekers, Dominique Schols, Paul Proost, Ghislain Opdenakker
Summary: Interleukin 7 (IL-7) plays a crucial role in T cell development, cancer, and autoimmune diseases. Abnormalities in IL-7 signaling are associated with T cell acute lymphoblastic leukemia (T-ALL) and involve interactions with matrix metalloproteinase-9 (MMP-9).
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Christoph Klenk, Leif Hommers, Martin J. Lohse
Summary: This study reveals that the extracellular domain of PTH1R is cleaved by metalloproteinases, leading to impaired stability of the receptor. The cleavage site is located in the first loop of the extracellular domain. A receptor mutant resistant to proteolytic cleavage showed reduced signaling to G(s) and increased activation of G(q).
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Multidisciplinary Sciences
Claire Chavarria, Lea Zaffalon, Sergio T. Ribeiro, Melanie Op, Manfredo Quadroni, Maria Sofia Iatrou, Chloe Chapuis, Fabio Martinon
Summary: This study reveals the significant regulatory role of the endoplasmic reticulum (ER) in NRF1 function, showing that it orchestrates NRF1 ubiquitination through the E3 ubiquitin ligase HRD1. RAD23A and RAD23B were identified as essential components of the DDI2 proteolytic machinery for NRF1 processing.
Article
Biochemistry & Molecular Biology
Tamara Rosell-Garcia, Sergio Rivas-Munoz, Alain Colige, Fernando Rodriguez-Pascual
Summary: Members of the lysyl oxidase (LOX) family catalyze the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin. Proteolysis by BMP1 and ADAMTS families regulates LOX enzymes, including LOXL1 associated with pelvic organ prolapse and pseudoexfoliation (PEX) glaucoma. This study reveals the molecular information of LOXL1 proteolysis by BMP1 and ADAMTS14, identifying the processing sites and suggesting complex regulation of LOXL1 function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
M. Ayse Tayman, Ismail Koyuncu
Summary: The mRNA expression of ADAMTS-1 is significantly increased in patients with periodontitis and is significantly correlated with clinical attachment level and probing pocket depth. However, there is no statistically significant difference in the mRNA expression of ADAMTS-9 and TIMP-3 between periodontitis patients and the control group. These findings suggest that metalloproteinases from the ADAMTS family are associated with the pathogenesis and progression of periodontal disease.
BIOTECHNIC & HISTOCHEMISTRY
(2023)
Review
Cell & Tissue Engineering
Priscila Anhel Medrano-Gonzalez, Osmar Rivera-Ramirez, Luis Felipe Montano, Erika P. Rendon-Huerta
Summary: CD44 is a transmembrane glycoprotein expressed in healthy and tumor tissues, with modifications in its structure affecting its activity, particularly through consecutive cleavage of its extracellular ectodomain by metalloproteases. This process generates biologically active substrates, contributing to the regulation of genes and proteins associated with cancer development.
STEM CELLS INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Laine Lysyk, Raelynn Brassard, Elena Arutyunova, Verena Siebert, Zhenze Jiang, Emmanuella Takyi, Melissa Morrison, Howard S. Young, Marius K. Lemberg, Anthony J. O'Donoghue, M. Joanne Lemieux
Summary: This study using recombinant PARL provides fundamental insights into its catalytic activity and substrate preferences, enhancing our understanding of its role in mitochondrial function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Salvatore Santamaria, Doretta Cuffaro, Elisa Nuti, Lidia Ciccone, Tiziano Tuccinardi, Francesca Liva, Felicia D'Andrea, Rens de Groot, Armando Rossello, Josefin Ahnstrom
Summary: ADAMTS-5 is a key protease involved in the turnover of proteoglycans, with dysregulated activity linked to osteoarthritis. A new class of sugar-based arylsulfonamides was designed based on ADAMTS-5's ability to bind beta-N-acetyl-D-glucosamine. The most promising compound, 4b, showed high selectivity over ADAMTS-4 as a non-zinc binding inhibitor targeting a previously unknown substrate-binding site critical for substrate recognition.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Kazuhiro Yamamoto, Rens de Groot, Simone Dario Scilabra, Hang Fai Kwok, Salvatore Santamaria
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Hematology
Chiara Pirillo, Flora Birch, Floriane S. Tissot, Sara Gonzalez Anton, Myriam Haltalli, Valentina Tini, Isabella Kong, Ben Partridge, Constandina Pospori, Karen Keeshan, Salvatore Santamaria, Edwin Hawkins, Brunangelo Falini, Andrea Marra, Delfim Duarte, Chiu Fan Lee, Edward Roberts, Cristina Lo Celso
Summary: By studying an experimental model of AML, it was found that AML may directly affect healthy cells through damaged blood vessels. By inhibiting the activity of matrix metalloproteinases (MMPs), the spread and invasion of AML can be reduced, the retention of healthy hematopoietic stem cells (HSPCs) in the bone marrow can be increased, and patient survival can be extended. This suggests that MMP inhibition could be a promising complementary therapy.
Article
Hematology
Adrienn Teraz-Orosz, Magdalena Gierula, Anastasis Petri, David Jones, Renos Keniyopoullos, Patricia Badia Folgado, Salvatore Santamaria, James T. B. Crawley, David A. Lane, Josefin Ahnstrom
Summary: Protein S is a cofactor that enhances the inhibition of factor XIII activity and generation by TFPI alpha. The interaction between TFPI alpha and protein S is critical for this enhancement, and binding of C4BP to protein S LG1 abolishes the TFPI cofactor function. The amino acids involved in TFPI alpha enhancement and the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S were investigated. It was found that Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 of protein S are critical for its function, and binding of the C4BP beta-chain blocks this function.
Article
Hematology
Jin-Sup Shin, Maryam Owais Subhan, Geraldine Cambridge, Yanping Guo, Rens de Groot, Marie Scully, Mari Thomas
Summary: Acute iTTP is characterized by dysregulation of B- and cTfh cell homeostasis with depletion of post-GC memory cells and cTfh cells and increased plasmablasts. Changes in CD80 expression on B cells further suggest altered interactions with T cells.
Article
Biochemistry & Molecular Biology
Kazuhiro Yamamoto, Carsten Scavenius, Maria M. Meschis, Abdulrahman M. E. Gremida, Emilie H. Mogensen, Ida B. Thogersen, Simone Bonelli, Simone D. Scilabra, Anders Jensen, Salvatore Santamaria, Josefin Ahnstrom, George Bou-Gharios, Jan J. Enghild, Hideaki Nagase
Summary: This study investigates the role of low-density lipoprotein receptor-related protein 1 (LRP1) in the endocytosis process of articular cartilage. By analyzing the LRP1 interactome, the researchers identified numerous ligand candidates and confirmed their direct binding to LRP1. They also found that inhibition of LRP1-ligand interaction resulted in cell death and alterations in the secretome and transcriptional profile of human chondrocytes. The study highlights the specificity and extent of the chondrocyte LRP1 ligandome and identifies potential new therapeutic targets for osteoarthritis.
Article
Hematology
Nithya Prasannan, Mari Thomas, Matthew Stubbs, John-Paul Westwood, Rens de Groot, Deepak Singh, Marie Scully
Summary: The benefits of caplacizumab in acute immune-mediated thrombotic thrombocytopenic purpura (iTTP) are well established. Delayed normalization of ADAMTS13 activity (>30%) was observed in a subgroup treated with caplacizumab, not seen in the precaplacizumab era. Patients treated with caplacizumab achieved ADAMTS13 activity >30% later than those without caplacizumab, and extended use of caplacizumab was associated with decreased ADAMTS13 activity response.
Letter
Hematology
Maryam Owais Subhan, Rens de Groot, Marie Scully
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Chemistry, Medicinal
Doretta Cuffaro, Lidia Ciccone, Armando Rossello, Elisa Nuti, Salvatore Santamaria
Summary: Osteoarthritis is a common degenerative joint disease. ADAMTS4 and ADAMTS5, members of the ADAMTS family, were identified in 1999 as the enzymes responsible for aggrecan degradation in cartilage. Zinc-chelating inhibitors targeting the active site showed disappointing results, leading to the exploration of exosite inhibitors. However, the lack of structural and functional data on aggrecanase exosites has hampered their potential development.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alexander Frederick Minns, Yawei Qi, Kazuhiro Yamamoto, Karen Lee, Salvatore Santamaria
Summary: ADAMTS1 is a protease involved in various physiological processes, and it interacts with multiple proteoglycan substrates. The proteoglycanase activity of ADAMTS1 is weaker than other family members, and the spacer and cysteine-rich domains are major determinants of its function. Additionally, these C-terminal domains are also involved in the proteolysis of other proteoglycans.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Marsioleda Kemberi, Yousuf Salmasi, Salvatore Santamaria
Summary: Thoracic aortic aneurysm and dissection (TAAD) are complex diseases that are difficult to diagnose early. The role of ADAMTSs in thoracic aortic disease and their potential use as biomarkers for diagnosis and disease progression are discussed in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Mary I. Underwood, Ferras Alwan, Mari R. Thomas, Marie A. Scully, James T. B. Crawley
Summary: Severe deficiency in ADAMTS-13 and loss of von Willebrand factor-cleaving function can cause microvascular thrombosis in patients with thrombotic thrombocytopenic purpura (TTP). Immune-mediated TTP (iTTP) is characterized by anti-ADAMTS-13 immunoglobulin G antibodies that inhibit ADAMTS-13 function and/or increase its clearance. Our study aims to investigate the role of antibody-mediated ADAMTS-13 clearance and inhibition in iTTP patients during plasma exchange (PEX) therapy.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Adela Constantinescu-Bercu, Anna Kessler, Rens de Groot, Bertina Dragunaite, Melissa Heightman, Toby Hillman, Laura C. Price, Ewan Brennan, Raphael Sivera, Karen Vanhoorelbeke, Deepak Singh, Marie Scully
Summary: This study used a microfluidic assay to investigate the thrombogenicity in patients with PCS and found significant platelet binding in these patients. Compared with the control group, patients with PCS showed increased thrombi volume related to platelet activity, thrombin generation, and VWF activity.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Salvatore Santamaria, Frederic Buemi, Elisa Nuti, Doretta Cuffaro, Elena De Vita, Tiziano Tuccinardi, Armando Rossello, Steven Howell, Shahid Mehmood, Ambrosius P. Snijders, Rens de Groot
Summary: ADAMTS-7 extracellular protease is considered a potential therapeutic target for atherosclerosis and coronary artery disease. A novel fluorescence substrate, ATS7FP7, was developed for high-throughput screening of ADAMTS-7 inhibitors, which may accelerate translational studies for treating cardiovascular diseases.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)