Selenium and selenocysteine: roles in cancer, health, and development.

The many biological and biomedical effects of selenium are relatively unknown outside the selenium field. This fascinating element, initially described as a toxin, was subsequently shown to be essential for health and development. By the mid-1990s selenium emerged as one of the most promising cancer chemopreventive agents, but subsequent human clinical trials yielded contradictory results. However, basic research on selenium continued to move at a rapid pace, elucidating its many roles in health, development, and in cancer prevention and promotion. Dietary selenium acts principally through selenoproteins, most of which are oxidoreductases involved in diverse cellular functions.

[1]  V. Gladyshev,et al.  Thioredoxin Reductase 1 Deficiency Reverses Tumor Phenotype and Tumorigenicity of Lung Carcinoma Cells* , 2006, Journal of Biological Chemistry.

[2]  A. Luke,et al.  Distribution and functional consequences of nucleotide polymorphisms in the 3'-untranslated region of the human Sep15 gene. , 2001, Cancer research.

[3]  V. Gladyshev,et al.  Biosynthesis of Selenocysteine on Its tRNA in Eukaryotes , 2006, PLoS biology.

[4]  L. Chavatte,et al.  Ribosomal protein L30 is a component of the UGA-selenocysteine recoding machinery in eukaryotes , 2005, Nature Structural &Molecular Biology.

[5]  Bruce W. Turnbull,et al.  Effects of Selenium Supplementation for Cancer Prevention in Patients With Carcinoma of the Skin: A Randomized Controlled Trial , 1996 .

[6]  V. Gladyshev,et al.  Selenocysteine incorporation machinery and the role of selenoproteins in development and health. , 2006, Progress in nucleic acid research and molecular biology.

[7]  B. Carlson,et al.  Hepatically derived selenoprotein P is a key factor for kidney but not for brain selenium supply. , 2005, The Biochemical journal.

[8]  Vadim N. Gladyshev,et al.  Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[9]  V. Gladyshev,et al.  Selective Rescue of Selenoprotein Expression in Mice Lacking a Highly Specialized Methyl Group in Selenocysteine tRNA* , 2005, Journal of Biological Chemistry.

[10]  Michael E. Budiman,et al.  Eukaryotic initiation factor 4a3 is a selenium-regulated RNA-binding protein that selectively inhibits selenocysteine incorporation. , 2009, Molecular cell.

[11]  V. Gladyshev,et al.  The Outcome of Selenium and Vitamin E Cancer Prevention Trial (SELECT) reveals the need for better understanding of selenium biology. , 2009, Molecular interventions.

[12]  V. Gladyshev,et al.  MsrB1 and MICALs regulate actin assembly and macrophage function via reversible stereoselective methionine oxidation. , 2013, Molecular cell.

[13]  R. Brigelius-Flohé,et al.  The selenoproteins GPx2, TrxR2 and TrxR3 are regulated by Wnt signalling in the intestinal epithelium. , 2012, Biochimica et biophysica acta.

[14]  V. Gladyshev,et al.  The Sep15 protein family: Roles in disulfide bond formation and quality control in the endoplasmic reticulum , 2007, IUBMB life.

[15]  J. F. Atkins,et al.  Deletion of Selenoprotein P Alters Distribution of Selenium in the Mouse* , 2003, The Journal of Biological Chemistry.

[16]  C. Davis,et al.  Selenoproteins Harboring a Split Personality in Both Preventing and Promoting Cancer , 2011 .

[17]  L. Flohé,et al.  Glutathione peroxidase: A selenoenzyme , 1973, FEBS letters.

[18]  K. W. Franke A new toxicant occurring naturally in certain samples of plant foodstuffs. 1. Results obtained in preliminary feeding trials. , 1934 .

[19]  C. Davis,et al.  Both selenoproteins and low molecular weight selenocompounds reduce colon cancer risk in mice with genetically impaired selenoprotein expression , 2006, The Journal of nutrition.

[20]  K. Esser,et al.  Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth. , 2003, The Journal of nutrition.

[21]  A. Krol,et al.  Evolutionarily different RNA motifs and RNA-protein complexes to achieve selenoprotein synthesis. , 2002, Biochimie.

[22]  R. Brigelius-Flohé,et al.  Activation of the glutathione peroxidase 2 (GPx2) promoter by β-catenin , 2007, Biological chemistry.

[23]  G. Fantuzzi,et al.  Selenoprotein deficiency enhances radiation-induced micronuclei formation. , 2008, Molecular nutrition & food research.

[24]  K. Schwarz,et al.  Factor 3 activity of selenium compounds. , 1958, The Journal of biological chemistry.

[25]  V. Gladyshev,et al.  Thioredoxin reductase 1 protects against chemically induced hepatocarcinogenesis via control of cellular redox homeostasis. , 2012, Carcinogenesis.

[26]  V. Ray,et al.  Selenoprotein deficiency accelerates prostate carcinogenesis in a transgenic model. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[27]  K. Mitsumori,et al.  Molecular Expression Analysis of β-Naphthoflavone-induced Hepatocellular Tumors in Rats , 2009, Toxicologic pathology.

[28]  B. Carlson,et al.  Prostate epithelium-specific deletion of the selenocysteine tRNA gene Trsp leads to early onset intraepithelial neoplasia. , 2014, The American journal of pathology.

[29]  R. Hurst,et al.  Selenium and vitamin E supplementation for cancer prevention. , 2009, JAMA.

[30]  G. Combs,et al.  The role of selenium in nutrition , 1986 .

[31]  R. Brigelius-Flohé,et al.  Glutathione Peroxidase 2 and Its Role in Cancer , 2011 .

[32]  S. Novoselov,et al.  Specific Excision of the Selenocysteine tRNA[Ser]Sec (Trsp) Gene in Mouse Liver Demonstrates an Essential Role of Selenoproteins in Liver Function* , 2004, Journal of Biological Chemistry.

[33]  C. Davis,et al.  Deficiency in the 15-kDa Selenoprotein Inhibits Tumorigenicity and Metastasis of Colon Cancer Cells , 2010, Cancer Prevention Research.

[34]  L. Schomburg,et al.  Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice. , 2008, The Biochemical journal.

[35]  C. Davis,et al.  Deficiency in the 15 kDa Selenoprotein Inhibits Human Colon Cancer Cell Growth , 2011, Nutrients.

[36]  Elias S. J. Arnér Focus on mammalian thioredoxin reductases--important selenoproteins with versatile functions. , 2009, Biochimica et biophysica acta.

[37]  V. Gladyshev,et al.  Selenocysteine in thiol/disulfide-like exchange reactions. , 2013, Antioxidants & redox signaling.

[38]  L. Schomburg,et al.  Thyroid function is maintained despite increased oxidative stress in mice lacking selenoprotein biosynthesis in thyroid epithelial cells. , 2012, Antioxidants & redox signaling.

[39]  J. Wootton,et al.  A New Human Selenium-containing Protein , 1998, The Journal of Biological Chemistry.

[40]  S. Gygi,et al.  Targeted insertion of cysteine by decoding UGA codons with mammalian selenocysteine machinery , 2010, Proceedings of the National Academy of Sciences.

[41]  E. Anderson Hudson et al. , 1977 .

[42]  Dieter Söll,et al.  RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea , 2006, Proceedings of the National Academy of Sciences.

[43]  R. Brigelius-Flohé,et al.  The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis , 2012, International journal of cell biology.

[44]  R. Brigelius-Flohé,et al.  Selenoproteins of the Glutathione Peroxidase Family , 2011 .

[45]  V. Gladyshev,et al.  Contrasting roles of dietary selenium and selenoproteins in chemically induced hepatocarcinogenesis. , 2013, Carcinogenesis.

[46]  B. Carlson,et al.  Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[47]  B. Hallgrímsson,et al.  Osteo-Chondroprogenitor–Specific Deletion of the Selenocysteine tRNA Gene, Trsp, Leads to Chondronecrosis and Abnormal Skeletal Development: A Putative Model for Kashin-Beck Disease , 2009, PLoS genetics.

[48]  P. Taylor,et al.  Prostate Cancer Prevention and the Selenium and Vitamin E Cancer Prevention Trial (SELECT): A Selenium Perspective , 2011 .

[49]  Michael E. Budiman,et al.  Nucleolin binds to a subset of selenoprotein mRNAs and regulates their expression , 2010, Nucleic acids research.

[50]  A. Böck,et al.  Selenocysteine: the 21st amino acid , 1991, Molecular microbiology.

[51]  C. Davis,et al.  Knockout of the 15 kDa Selenoprotein Protects against Chemically-Induced Aberrant Crypt Formation in Mice , 2012, PloS one.

[52]  A. Holmgren,et al.  Thioredoxin and thioredoxin reductase: current research with special reference to human disease. , 2010, Biochemical and biophysical research communications.

[53]  Jie Zhang,et al.  Roles of the 15-kDa Selenoprotein (Sep15) in Redox Homeostasis and Cataract Development Revealed by the Analysis of Sep 15 Knockout Mice* , 2011, The Journal of Biological Chemistry.

[54]  V. Gladyshev,et al.  Selenoproteins Are Essential for Proper Keratinocyte Function and Skin Development , 2010, PloS one.

[55]  B. Carlson,et al.  Selenoproteins reduce susceptibility to DMBA-induced mammary carcinogenesis. , 2012, Carcinogenesis.

[56]  A. Holmgren,et al.  The thioredoxin antioxidant system. , 2014, Free radical biology & medicine.

[57]  V. Gladyshev,et al.  Selenoproteins Mediate T Cell Immunity through an Antioxidant Mechanism* , 2008, Journal of Biological Chemistry.

[58]  Yang Liu,et al.  Recent advances in the development of thioredoxin reductase inhibitors as anticancer agents. , 2012, Current drug targets.

[59]  P. Harrison,et al.  The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the ‘termination’ codon, TGA. , 1986, The EMBO journal.

[60]  A. Diamond,et al.  Polymorphisms in Selenoprotein Genes and Cancer , 2011 .

[61]  K. Becker,et al.  On the potential of thioredoxin reductase inhibitors for cancer therapy. , 2006, Seminars in cancer biology.

[62]  T. Stadtman,et al.  Chemical characterization of the selenoprotein component of clostridial glycine reductase: identification of selenocysteine as the organoselenium moiety. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[63]  V. Gladyshev,et al.  Selective Restoration of the Selenoprotein Population in a Mouse Hepatocyte Selenoproteinless Background with Different Mutant Selenocysteine tRNAs Lacking Um34* , 2007, Journal of Biological Chemistry.

[64]  A. Böck,et al.  Nucleotide sequence and expression of the selenocysteine-containing polypeptide of formate dehydrogenase (formate-hydrogen-lyase-linked) from Escherichia coli. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[65]  V. Gladyshev,et al.  Evolution of selenium utilization traits , 2005, Genome Biology.

[66]  J. Crowley,et al.  Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). , 2009, JAMA.

[67]  V. Gladyshev,et al.  Comparative Genomics of Trace Element Dependence in Biology* , 2011, The Journal of Biological Chemistry.

[68]  S. Novoselov,et al.  Selenoprotein expression is essential in endothelial cell development and cardiac muscle function , 2007, Neuromuscular Disorders.

[69]  L. Flohé,et al.  Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues. , 2003, The Biochemical journal.

[70]  M. T. Howard,et al.  Translational Redefinition of UGA Codons Is Regulated by Selenium Availability* , 2013, The Journal of Biological Chemistry.

[71]  V. Gladyshev,et al.  Selenium and Selenoprotein Deficiencies Induce Widespread Pyogranuloma Formation in Mice, while High Levels of Dietary Selenium Decrease Liver Tumor Size Driven by TGFα , 2013, PloS one.

[72]  P. Hoffmann,et al.  The human selenoproteome: recent insights into functions and regulation , 2009, Cellular and Molecular Life Sciences.

[73]  V. Gladyshev,et al.  Thioredoxin reductase 1 deficiency enhances selenite toxicity in cancer cells via a thioredoxin-independent mechanism. , 2012, The Biochemical journal.

[74]  N. Copeland,et al.  Identification of a novel selD homolog from eukaryotes, bacteria, and archaea: is there an autoregulatory mechanism in selenocysteine metabolism? , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[75]  M. Berry,et al.  Recognition of UGA as a selenocysteine codon in Type I deiodinase requires sequences in the 3′ untranslated region , 1991, Nature.

[76]  U. Schweizer,et al.  Unveiling the molecular mechanisms behind selenium-related diseases through knockout mouse studies. , 2010, Antioxidants & redox signaling.

[77]  S. Jhanwar,et al.  Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype , 2004, Oncogene.

[78]  S. Florian,et al.  Deletion of Glutathione Peroxidase-2 Inhibits Azoxymethane-Induced Colon Cancer Development , 2013, PloS one.

[79]  V. Gladyshev,et al.  Selenoproteins regulate macrophage invasiveness and extracellular matrix-related gene expression , 2009, BMC Immunology.

[80]  R. Guigó,et al.  Characterization of Mammalian Selenoproteomes , 2003, Science.

[81]  S. Florian,et al.  Glutathione peroxidase-2 and selenium decreased inflammation and tumors in a mouse model of inflammation-associated carcinogenesis whereas sulforaphane effects differed with selenium supply. , 2012, Carcinogenesis.

[82]  E. Reszka,et al.  Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism , 2008, European journal of nutrition.

[83]  R. Burk,et al.  Selenoprotein P-expression, functions, and roles in mammals. , 2009, Biochimica et biophysica acta.

[84]  G. Kryukov,et al.  Selective Inhibition of Selenocysteine tRNA Maturation and Selenoprotein Synthesis in Transgenic Mice Expressing Isopentenyladenosine-Deficient Selenocysteine tRNA , 2001, Molecular and Cellular Biology.

[85]  C. Gobler,et al.  The central role of selenium in the biochemistry and ecology of the harmful pelagophyte, Aureococcus anophagefferens , 2013, The ISME Journal.

[86]  So Yeon Kwon,et al.  Structure-Expression Relationships of the 15-kDa Selenoprotein Gene , 2000, The Journal of Biological Chemistry.

[87]  V. Gladyshev,et al.  Eukaryotic selenoproteins and selenoproteomes. , 2009, Biochimica et biophysica acta.