Selenoproteins: Molecular Pathways and Physiological Roles

Abstract

Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by selenium-containing proteins (selenoproteins) that are present in all three domains of life. Although selenoproteins represent diverse molecular pathways and biological functions, all these proteins contain at least one selenocysteine (Sec), a seleniumcontaining amino acid, and most serve oxidoreductase functions. Sec is cotranslationally inserted into nascent polypeptide chains in response to the UGA codon, whose normal function is to terminate translation. To decode UGA as Sec, organisms evolved the Sec insertion machinery that allows incorporation of this amino acid at specific UGA codons in a process requiring a cis-acting Sec insertion sequence (SECIS) element. Although the basic mechanisms of Sec synthesis and insertion into proteins in both prokaryotes and eukaryotes have been studied in great detail, the identity and functions of many selenoproteins remain largely unknown. In the last decade, there has been significant progress in characterizing selenoproteins and selenoproteomes and understanding their physiological functions. We discuss current knowledge about how these unique proteins perform their functions at the molecular level and highlight new insights into the roles that selenoproteins play in human health.

Selenoprotein S-dependent Selenoprotein K Binding to p97(VCP) Protein Is Essential for Endoplasmic Reticulum-associated Degradation

“…However, the function of SelK during ERAD remains unclear. According to recent studies, SelS and SelK have been shown to associate with each other through their transmembrane domains, although the association might also involve additional proteins (24,43). In this study, p97(VCP) was required for the interaction of SelS with SelK (Fig.…”

The role of selenium in thyroid gland pathophysiology

“…A high activity of these enzymes has been demonstrated in the thyroid tissue; however, in order to maintain iodine metabolism, catalysed by deiodinases, and at an appropriate level, low activity of these enzymes will be enough, much lower than of other selenoproteins in the pathways of the metabolic turnover of proteins, fats, and amino acids [34,77,78]. Therefore, neither the concentration of selenium nor the concentrations of selenium-containing proteins directly influence the selenium content in the thyroid and the activity of selenoproteins contained in the TG [69,79].…”

Modulation of MHC class I surface expression in B16F10 melanoma cells by methylseleninic acid

“…3,4 The functional activity of selenoproteins might be due to their anti-oxidative effects or to an altered expression pattern of genes involved in cancer initiation and progression. 5,6 This was further strengthened by epidemiologic studies revealing an inverse correlation of the Se status and cancer incidence as well as cancer mortality. 7 Furthermore, Se is one of the few trace elements, for which anticarcinogenic effects have been proven in a randomized, double blinded, placebo controlled study.…”