Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-β signaling as primary targets

Autor: Edwin De Pauw, David J.S. Hulmes, Johanne Dubail, Catherine Moali, Laura Dupont, Sandrine Vadon-Le Goff, Mourad Bekhouche, Nicolas Smargiasso, Dominique Baiwir, Betty Nusgens, Frédéric Delolme, Isabelle Zanella-Cléon, Gabriel Mazzucchelli, Alain Colige, Cédric Leduc, Lauriane Janssen
Přispěvatelé: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Liège, Laboratory of Mass Spectrometry-GIGA-Proteomics, Laboratory of Mass Spectrometry, GIGA-R, Institut de biologie et chimie des protéines [Lyon] (IBCP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physical Chemistry and Mass Spectrometry Laboratory, GIGA-Cancer (CRCE), Centre Hospitalier Universitaire de Liège (CHU-Liège), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Cell signaling
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
Biochemistry
Extracellular matrix
03 medical and health sciences
ADAMTS Proteins
0302 clinical medicine
Transforming Growth Factor beta
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Genetics
Disintegrin
Humans
Molecular Biology
ComputingMilieux_MISCELLANEOUS
Adaptor Proteins
Signal Transducing
Thrombospondin
Metalloproteinase
ADAMTS
Extracellular Matrix
ADAMTS2
HEK293 Cells
030104 developmental biology
Gene Expression Regulation
Latent TGF-beta Binding Proteins
030220 oncology & carcinogenesis
biology.protein
Intercellular Signaling Peptides and Proteins
Proteoglycans
Chemokines
Procollagen N-Endopeptidase
Receptors
Transforming Growth Factor beta
Signal Transduction
Biotechnology
Extracellular matrix organization
Zdroj: FASEB Journal
FASEB Journal, Federation of American Society of Experimental Biology, 2016, 30 (5), pp.1741-1756. ⟨10.1096/fj.15-279869⟩
ISSN: 0892-6638
1530-6860
Popis: A disintegrin and metalloproteinase with thrombospondin type I motif (ADAMTS)2, 3, and 14 are collectively named procollagen N-proteinases (pNPs) because of their specific ability to cleave the aminopropeptide of fibrillar procollagens. Several reports also indicate that they could be involved in other biological processes, such as blood coagulation, development, and male fertility, but the potential substrates associated with these activities remain unknown. Using the recently described N-terminal amine isotopic labeling of substrate approach, we analyzed the secretomes of human fibroblasts and identified 8, 17, and 22 candidate substrates for ADAMTS2, 3, and 14, respectively. Among these newly identified substrates, many are components of the extracellular matrix and/or proteins related to cell signaling such as latent TGF-β binding protein 1, TGF-β RIII, and dickkopf-related protein 3. Candidate substrates for the 3 ADAMTS have been biochemically validated in different contexts, and the implication of ADAMTS2 in the control of TGF-β activity has been further demonstrated in human fibroblasts. Finally, the cleavage site specificity was assessed showing a clear and unique preference for nonpolar or slightly hydrophobic amino acids. This work shows that the activities of the pNPs extend far beyond the classically reported processing of the aminopropeptide of fibrillar collagens and that they should now be considered as multilevel regulators of matrix deposition and remodeling.-Bekhouche, M., Leduc, C., Dupont, L., Janssen, L., Delolme, F., Vadon-Le Goff, S., Smargiasso, N., Baiwir, D., Mazzucchelli, G., Zanella-Cleon, I., Dubail, J., De Pauw, E., Nusgens, B., Hulmes, D. J. S., Moali, C., Colige, A. Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-β signaling as primary targets.
Databáze: OpenAIRE
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