title: Extended interaction network of procollagen C-proteinase enhancer-1 in the extracellular matrix.
abstract: PCPE-1 (procollagen C-proteinase enhancer-1) is an extracellular matrix glycoprotein that can stimulate procollagen processing by procollagen C-proteinases such as BMP-1 (bone morphogenetic protein 1). PCPE-1 interacts with several proteins in addition to procollagens and BMP-1, suggesting that it could be involved in biological processes other than collagen maturation. We thus searched for additional partners of PCPE-1 in the extracellular matrix, which could provide new insights into its biological roles. We identified 17 new partners of PCPE-1 by SPR (surface plasmon resonance) imaging. PCPE-1 forms a transient complex with the β-amyloid peptide, whereas it forms high or very high affinity complexes with laminin-111 (KD=58.8 pM), collagen VI (KD=9.5 nM), TSP-1 (thrombospondin-1) (KD1=19.9 pM, KD2=14.5 nM), collagen IV (KD=49.4 nM) and endostatin, a fragment of collagen XVIII (KD1=0.30 nM, KD2=1.1 nM). Endostatin binds to the NTR (netrin-like) domain of PCPE-1 and decreases the degree of superstimulation of PCPE-1 enhancing activity by heparin. The analysis of the PCPE-1 interaction network based on Gene Ontology terms suggests that, besides its role in collagen deposition, PCPE-1 might be involved in tumour growth, neurodegenerative diseases and angiogenesis. In vitro assays have indeed shown that the CUB1CUB2 (where CUB is complement protein subcomponents C1r/C1s, urchin embryonic growth factor and BMP-1) fragment of PCPE-1 inhibits angiogenesis.
authors.affiliation: *UMR 5086 CNRS-Université Lyon 1, FR 3302 Institut de Biologie et Chimie des Protéines, 7 passage du Vercors, 69367 Lyon, Cedex 07, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Salza
authors.forename: Franck
authors.initials: F
authors.lastname: Peysselon
authors.forename: Emilie
authors.initials: E
authors.lastname: Chautard
authors.forename: Clément
authors.initials: C
authors.lastname: Faye
authors.forename: Laura
authors.initials: L
authors.lastname: Moschcovich
authors.forename: Tali
authors.initials: T
authors.lastname: Weiss
authors.forename: Laure
authors.initials: L
authors.lastname: Perrin-Cocon
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
authors.forename: Efrat
authors.initials: E
authors.lastname: Kessler
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ricard-Blum
mesh_terms: D002118:Calcium / Q000494:pharmacology; D043169:Endostatins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism*; D063990:Gene Ontology; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D018919:Neovascularization, Physiologic; D011485:Protein Binding / Q000187:drug effects; D060066:Protein Interaction Maps; D020349:Surface Plasmon Resonance
chemical_list: D043169:Endostatins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D046912:Multiprotein Complexes; C491555:PCOLCE protein, human; D006493:Heparin; D002118:Calcium