A Secreted Disulfide Catalyst Controls Extracellular Matrix Composition and Function

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Science  05 Jul 2013:
Vol. 341, Issue 6141, pp. 74-76
DOI: 10.1126/science.1238279

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Form and Function

The contribution of disulfide bonding to oxidative protein folding and assembly, quality control, and stress responses in the endoplasmic reticulum (ER) are widely recognized. In contrast, catalysis of disulfide bond formation downstream of the ER is uncharted territory. QSOX, a Golgi-localized or secreted disulfide catalyst, was identified in the 1970s and was more recently shown to be upregulated in many cancers. However, the physiological importance of QSOX catalytic activity has been unclear. Ilani et al. (p. 74, published online 23 May) found that human QSOX1 is essential for incorporation of laminin into the extracellular matrix, with profound effects on the capability of the matrix to support integrin-mediated cell adhesion and migration.


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.

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