Functions of the Late-Secretory Disulfide Catalyst QSOX

Quiescin Sulfhydryl Oxidase 1 (QSOX1) is a disulfide catalyst with an atypical localization. While disulfide bond formation in secretory proteins is carried out by multiple enzyme families and occurs primarily in the endoplasmic reticulum, QSOX1 is localized to the Golgi apparatus. Moreover, QSOX1 undergoes regulated secretion from quiescent fibroblasts and is over-produced in many adenocarcinomas. We have found that QSOX1 is required for incorporation of particular laminin isoforms into the basement membrane extracellular matrix (ECM) synthesized by fibroblasts. ECM produced without QSOX1 shows additional ultrastructural defects and fails to support the adherence and migration of tumor-derived epithelial cells in co-culture. We have indications that QSOX1 may have additional, intracellular targets as well.