title: A secreted disulfide catalyst controls extracellular matrix composition and function.
abstract: Disulfide bond formation in secretory proteins occurs primarily in the endoplasmic reticulum (ER), where multiple enzyme families catalyze cysteine cross-linking. Quiescin sulfhydryl oxidase 1 (QSOX1) is an atypical disulfide catalyst, localized to the Golgi apparatus or secreted from cells. We examined the physiological function for extracellular catalysis of de novo disulfide bond formation by QSOX1. QSOX1 activity was required for incorporation of laminin into the extracellular matrix (ECM) synthesized by fibroblasts, and ECM produced without QSOX1 was defective in supporting cell-matrix adhesion. We developed an inhibitory monoclonal antibody against QSOX1 that could modulate ECM properties and undermine cell migration.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel. tal.ilani@weizmann.ac.il
authors.forename: Tal
authors.initials: T
authors.lastname: Ilani
authors.forename: Assaf
authors.initials: A
authors.lastname: Alon
authors.forename: Iris
authors.initials: I
authors.lastname: Grossman
authors.forename: Ben
authors.initials: B
authors.lastname: Horowitz
authors.forename: Elena
authors.initials: E
authors.lastname: Kartvelishvily
authors.forename: Sidney R
authors.initials: SR
authors.lastname: Cohen
authors.forename: Deborah
authors.initials: D
authors.lastname: Fass
mesh_terms: D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D005109:Extracellular Matrix / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D005347:Fibroblasts / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D007797:Laminin / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D004220:Disulfides; D007797:Laminin; D050862:Oxidoreductases Acting on Sulfur Group Donors; C117183:QSOX1 protein, human; D003545:Cysteine