The 15-kDa selenoprotein (Sep15): functional analysis and role in cancer

The 15-kDa selenoprotein (Sep15) was identified several years ago as a protein of unknown function. In recent years, several lines of evidence implicated Sepl5 in the effect of dietary selenium in cancer prevention. These lines of evidence include: 1) protein expression patterns in normal and malignant cells; 2) identification of polymorphic sites that regulate Sep15 levels and differentially respond to selenium supplementation; 3) location of the Sep15 gene in the human genome; and 4) correlation between Sep15 haplotype and susceptibility to cancer. Functional analyses revealed a specific interaction between Sep15 and a protein folding sensor in the endoplasmic reticulum of mammalian cells and identified Sep15 as a novel thioredoxin-like fold redox regulator. Sep15 defines a new protein family that occurs in several organisms from green algae to mammals and also contains selenoprotein M (SelM) and a recently identified fish-specific selenoprotein Fep15