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

The 15-kDa selenoprotein (Sep15): functional analysis and role in cancer" (2006). Vadim Gladyshev Publications. Paper 41. Summary: The 15-kDa selenoprotein (Sepl5) 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 Sepl 5 levels and differentially respond to selenium supplementation; 3) location of the Sepl5 gene in the human genome; and 4) correlation between Sepl5 haplotype and susceptibility to cancer. Functional analyses revealed a specific interaction between Sep 15 and a protein folding sensor in the endoplasmic reticulum of mammalian cells and identified Sep 15 as a novel thioredoxin-like fold redox regulator. Sep 1 5 defines a new protein family that occurs in several organisms fiom green algae to mammals and also contains selenoprotein M (SelM) and a recently identified fish-specific selenoprotein Fep 15. Introduction Selenium, an important micronutrient, has been implicated in reducing the incidence of cancer in different animal models and human clinical trials [I-31. As discussed in many chapters in this book, this trace element is incorporated into proteins in the form of selenocysteine and is often present at the active centers of selenium-containing enzymes. This chapter describes one such protein, designated the 1 5-kDa selenoprotein (Sep 1 5). Sep 1 5 was identified in 1998 by purifLing and characterizing a protein fiom human T cells [4]. This protein was subsequently implicated in the cancer prevention effect of dietary selenium [5], and more recently in regulation of redox homeostasis in the endoplasmic reticulum (ER) [6]. This chapter provides up to date information on Sepl5 and members of its family.