The Structure of the Mouse Glutathione Peroxidase Gene: the Selenocysteine in the Active Site is Encoded by the 'termination' Codon, TGA

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1986 Jun 1

PMID 3015592

Citations 142

Authors

I Chambers

J Frampton

P Goldfarb

N Affara

W McBain

P R Harrison

Affiliations

Soon will be listed here.

Abstract

Glutathione peroxidase (GSHPx) is an important selenium-containing enzyme which protects cells from peroxide damage and also has a role in leukotriene formation. We report the identification of a genomic recombinant as encoding the entire mouse GSHPx gene. Surprisingly, the selenocysteine in the active site of the enzyme is encoded by TGA: this has been confirmed by primer extension/dideoxy sequencing experiments using reticulocyte mRNA. The same site of transcription initiation is used in three tissues in which the GSHPx mRNA is expressed at high levels (erythroblast, liver and kidney). Like some other regulated 'house-keeping' genes, the GSHPx gene has Sp1 binding site consensus sequences but no 'ATA' and 'CAAT' consensus sequences upstream of the transcription initiation site. Moreover, there is a cluster of two Sp1 binding site consensus sequences and two SV40 core enhancer sequences in the 3' region of the gene, close to the previously mapped position of a DNase I-hypersensitive site found only in tissues expressing the GSHPx mRNA at high levels.

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References

Nirenberg M, Caskey T, Marshall R, Brimacombe R, Kellogg D, Doctor B . The RNA code and protein synthesis. Cold Spring Harb Symp Quant Biol. 1966; 31:11-24. DOI: 10.1101/sqb.1966.031.01.008. View

Harrison P . Molecular analysis of erythropoiesis. A current appraisal. Exp Cell Res. 1984; 155(2):321-44. DOI: 10.1016/0014-4827(84)90194-0. View

Hodgson E, Fridovich I . The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: inactivation of the enzyme. Biochemistry. 1975; 14(24):5294-9. DOI: 10.1021/bi00695a010. View

Young P, Kaiser I . Aminoacylation of Escherichia coli cysteine tRNA by selenocysteine. Arch Biochem Biophys. 1975; 171(2):483-9. DOI: 10.1016/0003-9861(75)90057-0. View

Cone J, del Rio R, Davis J, STADTMAN T . Chemical characterization of the selenoprotein component of clostridial glycine reductase: identification of selenocysteine as the organoselenium moiety. Proc Natl Acad Sci U S A. 1976; 73(8):2659-63. PMC: 430707. DOI: 10.1073/pnas.73.8.2659. View

Yasuda M, Fujita T . Effect of lipid peroxidation on phospholipase A2 activity of rat liver mitochondria. Jpn J Pharmacol. 1977; 27(3):429-35. DOI: 10.1254/jjp.27.429. View

Berk A, Sharp P . Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977; 12(3):721-32. DOI: 10.1016/0092-8674(77)90272-0. View

SANGER F, Nicklen S, Coulson A . DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977; 74(12):5463-7. PMC: 431765. DOI: 10.1073/pnas.74.12.5463. View

SANGER F, Coulson A . The use of thin acrylamide gels for DNA sequencing. FEBS Lett. 1978; 87(1):107-10. DOI: 10.1016/0014-5793(78)80145-8. View

10.

Patek P, Collins J, Cohn M . Transformed cell lines susceptible or resistant to in vivo surveillance against tumorigenesis. Nature. 1978; 276(5687):510-1. DOI: 10.1038/276510a0. View

11.

Hamlyn P, Browniee G, Cheng C, Gait M, Milstein C . Complete sequence of constant and 3' noncoding regions of an immunoglobulin mRNA using the dideoxynucleotide method of RNA sequencing. Cell. 1978; 15(3):1067-75. DOI: 10.1016/0092-8674(78)90290-8. View

12.

RAPOPORT S, Schewe T, Wiesner R, Halangk W, Ludwig P, Tannert C . The lipoxygenase of reticulocytes. Purification, characterization and biological dynamics of the lipoxygenase; its identity with the respiratory inhibitors of the reticulocyte. Eur J Biochem. 1979; 96(3):545-61. DOI: 10.1111/j.1432-1033.1979.tb13068.x. View

13.

Jones J, Dilworth G, STADTMAN T . Occurrence of selenocysteine in the selenium-dependent formate dehydrogenase of Methanococcus vannielii. Arch Biochem Biophys. 1979; 195(2):255-60. DOI: 10.1016/0003-9861(79)90351-5. View

14.

Geller A, Rich A . A UGA termination suppression tRNATrp active in rabbit reticulocytes. Nature. 1980; 283(5742):41-6. DOI: 10.1038/283041a0. View

15.

Weaver R, Weissmann C . Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. Nucleic Acids Res. 1979; 7(5):1175-93. PMC: 342295. DOI: 10.1093/nar/7.5.1175. View

16.

Chirgwin J, Przybyla A, MacDonald R, Rutter W . Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979; 18(24):5294-9. DOI: 10.1021/bi00591a005. View

17.

Maxam A, Gilbert W . Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980; 65(1):499-560. DOI: 10.1016/s0076-6879(80)65059-9. View

18.

Bryant R, BAILEY J . Role of selenium-dependent glutathione peroxidase in platelet lipoxygenase metabolism. Prog Lipid Res. 1981; 20:189-94. DOI: 10.1016/0163-7827(81)90035-7. View

19.

Bryant R, Simon T, BAILEY J . Role of glutathione peroxidase and hexose monophosphate shunt in the platelet lipoxygenase pathway. J Biol Chem. 1982; 257(24):14937-43. View

20.

Condell R, Tappel A . Amino acid sequence around the active-site selenocysteine of rat liver glutathione peroxidase. Biochim Biophys Acta. 1982; 709(2):304-9. DOI: 10.1016/0167-4838(82)90472-1. View