Home > Publications Database > Dissecting the interaction between tissue inhibitor of metalloproteinases-3 (TIMP-3) and low density lipoprotein receptor-related protein-1 (LRP-1): Development of a 'TRAP' to increase levels of TIMP-3 in the tissue. > print

001     139205
005     20240321220555.0
024 7 _ |a 10.1016/j.matbio.2016.07.004
|2 doi
024 7 _ |a pmid:27476612
|2 pmid
024 7 _ |a 0945-053X
|2 ISSN
024 7 _ |a 1569-1802
|2 ISSN
037 _ _ |a DZNE-2020-05527
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Scilabra, Simone D
|0 P:(DE-2719)2811733
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|u dzne
245 _ _ |a Dissecting the interaction between tissue inhibitor of metalloproteinases-3 (TIMP-3) and low density lipoprotein receptor-related protein-1 (LRP-1): Development of a 'TRAP' to increase levels of TIMP-3 in the tissue.
260 _ _ |a Amsterdam [u.a.]
|c 2017
|b Elsevier
264 _ 1 |3 print
|2 Crossref
|b Elsevier BV
|c 2017-05-01
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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|s 1708603321_31171
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Tissue inhibitor of metalloproteinases 3 (TIMP-3) is a key regulator of extracellular matrix turnover for its ability to inhibit matrix metalloproteinases (MMPs), adamalysin-like metalloproteinases (ADAMs) and ADAMs with thrombospondin motifs (ADAMTSs). TIMP-3 is a secreted protein whose extracellular levels are regulated by endocytosis via the low-density-lipoprotein receptor-related protein-1 (LRP-1). In this study we developed a molecule able to 'trap' TIMP-3 extracellularly, thereby increasing its tissue bioavailability. LRP-1 contains four ligand-binding clusters. In order to investigate the TIMP-3 binding site on LRP-1, we generated soluble minireceptors (sLRPs) containing the four distinct binding clusters or part of each cluster. We used an array of biochemical methods to investigate the binding of TIMP-3 to different sLRPs. We found that TIMP-3 binds to the ligand-binding cluster II of the receptor with the highest affinity and a soluble minireceptor containing the N-terminal half of cluster II specifically blocked TIMP-3 internalization, without affecting the turnover of metalloproteinases. Mass spectrometry-based secretome analysis showed that this minireceptor, named T3TRAP, selectively increased TIMP-3 levels in the extracellular space and inhibited constitutive shedding of a number of cell surface proteins. In conclusion, T3TRAP represents a biological tool that can be used to modulate TIMP-3 levels in the tissue and could be potentially developed as a therapy for diseases characterized by a deficit of TIMP-3, including arthritis.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
|0 G:(DE-HGF)POF3-342
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|f POF III
|x 0
542 _ _ |i 2017-05-01
|2 Crossref
|u https://www.elsevier.com/tdm/userlicense/1.0/
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a LRP1 protein, human
|2 NLM Chemicals
650 _ 7 |a Low Density Lipoprotein Receptor-Related Protein-1
|2 NLM Chemicals
650 _ 7 |a Receptors, Artificial
|2 NLM Chemicals
650 _ 7 |a Recombinant Proteins
|2 NLM Chemicals
650 _ 7 |a TIMP3 protein, human
|2 NLM Chemicals
650 _ 7 |a Tissue Inhibitor of Metalloproteinase-3
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Binding Sites
|2 MeSH
650 _ 2 |a COS Cells
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Chlorocebus aethiops
|2 MeSH
650 _ 2 |a Endocytosis
|2 MeSH
650 _ 2 |a Epithelial Cells: cytology
|2 MeSH
650 _ 2 |a Epithelial Cells: metabolism
|2 MeSH
650 _ 2 |a Extracellular Matrix: chemistry
|2 MeSH
650 _ 2 |a Extracellular Matrix: metabolism
|2 MeSH
650 _ 2 |a Gene Expression Regulation
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Kinetics
|2 MeSH
650 _ 2 |a Low Density Lipoprotein Receptor-Related Protein-1: genetics
|2 MeSH
650 _ 2 |a Low Density Lipoprotein Receptor-Related Protein-1: metabolism
|2 MeSH
650 _ 2 |a Molecular Sequence Annotation
|2 MeSH
650 _ 2 |a Neuroglia: cytology
|2 MeSH
650 _ 2 |a Neuroglia: metabolism
|2 MeSH
650 _ 2 |a Protein Binding
|2 MeSH
650 _ 2 |a Protein Interaction Domains and Motifs
|2 MeSH
650 _ 2 |a Protein Interaction Mapping
|2 MeSH
650 _ 2 |a Protein Transport
|2 MeSH
650 _ 2 |a Receptors, Artificial: genetics
|2 MeSH
650 _ 2 |a Receptors, Artificial: metabolism
|2 MeSH
650 _ 2 |a Recombinant Proteins: genetics
|2 MeSH
650 _ 2 |a Recombinant Proteins: metabolism
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
650 _ 2 |a Solubility
|2 MeSH
650 _ 2 |a Tissue Inhibitor of Metalloproteinase-3: genetics
|2 MeSH
650 _ 2 |a Tissue Inhibitor of Metalloproteinase-3: metabolism
|2 MeSH
650 _ 2 |a Transfection
|2 MeSH
700 1 _ |a Yamamoto, Kazuhiro
|0 P:(DE-HGF)0
|b 1
700 1 _ |a Pigoni, Martina
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700 1 _ |a Sakamoto, Kazuma
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700 1 _ |a Müller, Stephan A
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700 1 _ |a Papadopoulou, Alkmini
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700 1 _ |a Lichtenthaler, Stefan F
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700 1 _ |a Troeberg, Linda
|0 P:(DE-HGF)0
|b 7
700 1 _ |a Nagase, Hideaki
|0 P:(DE-HGF)0
|b 8
700 1 _ |a Kadomatsu, Kenji
|0 P:(DE-HGF)0
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773 1 8 |a 10.1016/j.matbio.2016.07.004
|b : Elsevier BV, 2017-05-01
|p 69-79
|3 journal-article
|2 Crossref
|t Matrix Biology
|v 59
|y 2017
|x 0945-053X
773 _ _ |a 10.1016/j.matbio.2016.07.004
|g Vol. 59, p. 69 - 79
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856 4 _ |u https://pub.dzne.de/record/139205/files/DZNE-2020-05527_Restricted.pdf
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