QSOX1
QSOX1 (quiescin sulfhydryl oxidase 1) is the secreted enzyme that inserts disulfide bonds into extracellular-matrix proteins — the oxidase that finishes folding collagen, laminin, and other matrix components after they leave the cell.
Function
QSOX1 catalyzes disulfide-bond formation using a thioredoxin domain to accept electrons from client-protein thiols, a shuttle domain to move them, and an FAD-dependent oxidase domain to hand them to oxygen. It is the only enzyme known to introduce disulfide bonds into proteins outside the cell and independent of the Ero1–PDI machinery of the ER. Its substrates are matrix and basement-membrane proteins, and its secretion is driven by quiescence signals — the gene’s name records its discovery in quiescent fibroblasts. Matrix stiffness and crosslinking are QSOX1 outputs, which places the enzyme in the machinery that determines the mechanical environment a cell lives in.
In cancer
QSOX1’s tumor role is tissue-dependent. In pancreatic and breast cancer it promotes invasion and matrix remodeling, and high expression correlates with poor prognosis; stromal QSOX1 stiffens the matrix that TAZ mechanotransduction reads. In other contexts QSOX1 suppresses tumor growth — it is downregulated in some hepatocellular carcinomas — and it has a documented role in the fibroblast quiescence that its discovery reflected.
Notes
- Human gene symbol: QSOX1; UniProt O00391; 747 amino acids; thioredoxin, Erv/ALR, and HRR domains.