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Vadim N. Gladyshev - One of the best experts on this subject based on the ideXlab platform.
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Selenoproteins in colon cancer
Free Radical Biology and Medicine, 2018Co-Authors: Kristin M. Peters, Bradley A. Carlson, Vadim N. Gladyshev, Petra A. TsujiAbstract:Abstract Selenocysteine-containing proteins (Selenoproteins) have been implicated in the regulation of various cell signaling pathways, many of which are linked to colorectal malignancies. In this in-depth excurse into the selenoprotein literature, we review possible roles for human Selenoproteins in colorectal cancer, focusing on the typical hallmarks of cancer cells and their tumor-enabling characteristics. Human genome studies of single nucleotide polymorphisms in various genes coding for Selenoproteins have revealed potential involvement of glutathione peroxidases, thioredoxin reductases, and other proteins. Cell culture studies with targeted down-regulation of Selenoproteins and studies utilizing knockout/transgenic animal models have helped elucidate the potential roles of individual Selenoproteins in this malignancy. Those Selenoproteins, for which strong links to development or progression of colorectal cancer have been described, may be potential future targets for clinical interventions.
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selenoprotein gene nomenclature
Journal of Biological Chemistry, 2016Co-Authors: Raymond F. Burk, Brigelius Flohe Regina, Sergi Castellano, Elspeth A Bruford, Elias S J Arner, Bradley A. Carlson, Vadim N. Gladyshev, Marla J Berry, Laurent ChavatteAbstract:Abstract The human genome contains 25 genes coding for selenocysteine-containing proteins (Selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to Selenoproteins across vertebrates.
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selenoprotein gene nomenclature
Journal of Biological Chemistry, 2016Co-Authors: Raymond F. Burk, Brigelius Flohe Regina, Sergi Castellano, Elspeth A Bruford, Elias S J Arner, Bradley A. Carlson, Vadim N. Gladyshev, Marla J Berry, Laurent ChavatteAbstract:Abstract The human genome contains 25 genes coding for selenocysteine-containing proteins (Selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to Selenoproteins across vertebrates.
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secisearch3 and seblastian new tools for prediction of secis elements and Selenoproteins
Nucleic Acids Research, 2013Co-Authors: Marco Mariotti, Roderic Guigo, Alexei V Lobanov, Vadim N. GladyshevAbstract:Selenoproteins are proteins containing an uncommon amino acid selenocysteine (Sec). Sec is inserted by a specific translational machinery that recognizes a stem-loop structure, the SECIS element, at the 3' UTR of selenoprotein genes and recodes a UGA codon within the coding sequence. As UGA is normally a translational stop signal, Selenoproteins are generally misannotated and designated tools have to be developed for this class of proteins. Here, we present two new computational methods for selenoprotein identification and analysis, which we provide publicly through the web servers at http://gladyshevlab.org/SelenoproteinPredictionServer or http://seblastian.crg.es. SECISearch3 replaces its predecessor SECISearch as a tool for prediction of eukaryotic SECIS elements. Seblastian is a new method for selenoprotein gene detection that uses SECISearch3 and then predicts selenoprotein sequences encoded upstream of SECIS elements. Seblastian is able to both identify known Selenoproteins and predict new Selenoproteins. By applying these tools to diverse eukaryotic genomes, we provide a ranked list of newly predicted Selenoproteins together with their annotated cysteine-containing homologues. An analysis of a representative candidate belonging to the AhpC family shows how the use of Sec in this protein evolved in bacterial and eukaryotic lineages.
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understanding selenoprotein function and regulation through the use of rodent models
Biochimica et Biophysica Acta, 2012Co-Authors: Marina V Kasaikina, Dolph L Hatfield, Vadim N. GladyshevAbstract:Abstract Selenium (Se) is an essential micronutrient. Its biological functions are associated with Selenoproteins, which contain this trace element in the form of the 21st amino acid, selenocysteine. Genetic defects in selenocysteine insertion into proteins are associated with severe health issues. The consequences of selenoprotein deficiency are more variable, with several Selenoproteins being essential, and several showing no clear phenotypes. Much of these functional studies benefited from the use of rodent models and diets employing variable levels of Se. This review summarizes the data obtained with these models, focusing on mouse models with targeted expression of individual Selenoproteins and removal of individual, subsets or all Selenoproteins in a systemic or organ-specific manner. This article is part of a Special Issue entitled: Cell Biology of Metals.
Bradley A. Carlson - One of the best experts on this subject based on the ideXlab platform.
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Selenoproteins in colon cancer
Free Radical Biology and Medicine, 2018Co-Authors: Kristin M. Peters, Bradley A. Carlson, Vadim N. Gladyshev, Petra A. TsujiAbstract:Abstract Selenocysteine-containing proteins (Selenoproteins) have been implicated in the regulation of various cell signaling pathways, many of which are linked to colorectal malignancies. In this in-depth excurse into the selenoprotein literature, we review possible roles for human Selenoproteins in colorectal cancer, focusing on the typical hallmarks of cancer cells and their tumor-enabling characteristics. Human genome studies of single nucleotide polymorphisms in various genes coding for Selenoproteins have revealed potential involvement of glutathione peroxidases, thioredoxin reductases, and other proteins. Cell culture studies with targeted down-regulation of Selenoproteins and studies utilizing knockout/transgenic animal models have helped elucidate the potential roles of individual Selenoproteins in this malignancy. Those Selenoproteins, for which strong links to development or progression of colorectal cancer have been described, may be potential future targets for clinical interventions.
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Radioactive 75 Se Labeling and Detection of Selenoproteins
Methods in molecular biology (Clifton N.J.), 2017Co-Authors: Ryuta Tobe, Anton A. Turanov, Bradley A. CarlsonAbstract:The trace element selenium (Se) is incorporated into proteins as the amino acid selenocysteine (Sec), which is cotranslationally inserted into specific proteins in response to a UGA codon. Proteins containing Sec at these specific positions are called Selenoproteins. Most Selenoproteins function as oxidoreductases, while some serve other important functions. There are 25 known selenoprotein genes in humans and 24 in mice. The use of Sec allows Selenoproteins to be detected by a convenient method involving metabolic labeling with 75Se. Labeling of cells and whole animals are used for the examination of selenoprotein expression profiles and the investigation of selenoprotein functions. In mammals, nonspecific 75Se insertion is very low, and sensitivity and specificity of selenoprotein detection approaches that of Western blotting. This method allows for the examination of selenoprotein expression and Se metabolism in model and non-model organisms. Herein, we describe experimental protocols for analyzing Selenoproteins by metabolic labeling with 75Se both in vitro and in vivo. As an example, the procedure for metabolic labeling of HEK293T human embryonic kidney cells is described in detail. This approach remains a method of choice for the detection of Selenoproteins in diverse settings.
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selenoprotein gene nomenclature
Journal of Biological Chemistry, 2016Co-Authors: Raymond F. Burk, Brigelius Flohe Regina, Sergi Castellano, Elspeth A Bruford, Elias S J Arner, Bradley A. Carlson, Vadim N. Gladyshev, Marla J Berry, Laurent ChavatteAbstract:Abstract The human genome contains 25 genes coding for selenocysteine-containing proteins (Selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to Selenoproteins across vertebrates.
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selenoprotein gene nomenclature
Journal of Biological Chemistry, 2016Co-Authors: Raymond F. Burk, Brigelius Flohe Regina, Sergi Castellano, Elspeth A Bruford, Elias S J Arner, Bradley A. Carlson, Vadim N. Gladyshev, Marla J Berry, Laurent ChavatteAbstract:Abstract The human genome contains 25 genes coding for selenocysteine-containing proteins (Selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to Selenoproteins across vertebrates.
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mutation in human selenocysteine transfer rna selectively disrupts selenoprotein synthesis
Journal of Clinical Investigation, 2016Co-Authors: Erik Schoenmakers, Bradley A. Carlson, Ryuta Tobe, Maura Agostini, Carla Moran, O Rajanayagam, Elena G Bochukova, Rachel Peat, Evelien Gevers, F MuntoniAbstract:of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress-related, but not housekeeping, Selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress-related selenoprotein production is likely mediated by reduced expression and diminished 2′-O-methylribosylation at uridine 34 in mutant tRNA [Ser]Sec . Moreover, this methylribosylation defect was restored by cellular complementation with normal tRNA [Ser]Sec . This study identifies a tRNA mutation that selectively impairs synthesis of stress-related Selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis.
Dolph L Hatfield - One of the best experts on this subject based on the ideXlab platform.
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understanding selenoprotein function and regulation through the use of rodent models
Biochimica et Biophysica Acta, 2012Co-Authors: Marina V Kasaikina, Dolph L Hatfield, Vadim N. GladyshevAbstract:Abstract Selenium (Se) is an essential micronutrient. Its biological functions are associated with Selenoproteins, which contain this trace element in the form of the 21st amino acid, selenocysteine. Genetic defects in selenocysteine insertion into proteins are associated with severe health issues. The consequences of selenoprotein deficiency are more variable, with several Selenoproteins being essential, and several showing no clear phenotypes. Much of these functional studies benefited from the use of rodent models and diets employing variable levels of Se. This review summarizes the data obtained with these models, focusing on mouse models with targeted expression of individual Selenoproteins and removal of individual, subsets or all Selenoproteins in a systemic or organ-specific manner. This article is part of a Special Issue entitled: Cell Biology of Metals.
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Selenoproteins reduce susceptibility to dmba induced mammary carcinogenesis
Carcinogenesis, 2012Co-Authors: Tamaro Hudson, Bradley A. Carlson, Dolph L Hatfield, Lorraine M Sordillo, Mark J Hoeneroff, Heather A Young, William J Muller, Jeffrey E GreenAbstract:Selenium is an essential micronutrient in the diet of humans and other mammals. Based largely on animal studies and epidemiological evidence, selenium is purported to be a promising cancer chemopreventive agent. However, the biological mechanisms by which chemopreventive activity takes place are poorly understood. It remains unclear whether selenium acts in its elemental form, through incorporation into organic compounds, through Selenoproteins or any combination of these. The purpose of this study was to determine whether Selenoproteins mitigate the risk of developing chemically induced mammary cancer. Selenoprotein expression was ablated in mouse mammary epithelial cells through genetic deletion of the selenocysteine (Sec) tRNA gene (Trsp), whose product, designated selenocysteine tRNA, is required for selenoprotein translation. Trsp floxed and mouse mammary tumor virus (MMTV)-cre mice were crossed to achieve tissue-specific excision of Trsp in targeted mammary glands. Eight- to twelve-week-old second generation Trsp(fl/+);wt, Trsp(fl/+);MMTV-cre, Trsp(fl/fl);wt and Trsp(fl/fl);MMTV-cre female mice were administered standard doses of the carcinogen, 7,12-dimethylbenzylbenz[a]antracene. Our results revealed that heterozygous, Trsp(fl/+);MMTV-cre mice showed no difference in tumor incidence, tumor rate and survival compared with the Trsp(fl/+);wt mice. However, 54.8% of homozygous Trsp(fl/f)(l);MMTV-cre mice developed mammary tumors and exhibited significantly shorter survival than the corresponding Trsp(fl/fl);wt mice, where only 36.4% developed tumors. Loss of the homozygous Trsp alleles was associated with the reduction of selenoprotein expression. The results suggest that mice with reduced selenoprotein expression have increased susceptibility to developing carcinogen-induced mammary tumors and that a major protective mechanism against carcinogen-induced mammary cancer requires the expression of these Selenoproteins.
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Analyses of fruit flies that do not express Selenoproteins or express the mouse selenoprotein, methionine sulfoxide reductase B1,reveal a role of Selenoproteins in stress resistance
2011Co-Authors: Valentina A. Shchedrina, Gerd Vorbruggen, Mitsuko Hirosawa-Takamori, Anton A. Turanov, Hadise Kabil, Lawrence G Harshman, Byeong Jae Lee, Dolph L Hatfield, Hwa Young Kim, Vadim N. GladyshevAbstract:Selenoproteins are essential in vertebrates because of their crucial role in cellular redox homeostasis, but some invertebrates that lack Selenoproteins have recently been identified. Genetic disruption of selenoprotein biosynthesis had no effect on lifespan and oxidative stress resistance of Drosophila melanogaster. In the current study, fruit flies with knock-out of the selenocysteine-specific elongation factor were metabolically labeled with (75)Se; they did not incorporate selenium into proteins and had the same lifespan on a chemically defined diet with or without selenium supplementation. These flies were, however, more susceptible to starvation than controls, and this effect could be ascribed to the function of selenoprotein K. We further expressed mouse methionine sulfoxide reductase B1 (MsrB1), a selenoenzyme that catalyzes the reduction of oxidized methionine residues and has protein repair function, in the whole body or the nervous system of fruit flies. This exogenous selenoprotein could only be expressed when the Drosophila selenocysteine insertion sequence element was used, whereas the corresponding mouse element did not support selenoprotein synthesis. Ectopic expression of MsrB1 in the nervous system led to an increase in the resistance against oxidative stress and starvation, but did not affect lifespan and reproduction, whereas ubiquitous MsrB1 expression had no effect. Dietary selenium did not influence lifespan of MsrB1-expressing flies. Thus, in contrast to vertebrates, fruit flies preserve only three Selenoproteins, which are not essential and play a role only under certain stress conditions, thereby limiting the use of the micronutrient selenium by these organisms.
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Selenoproteins are essential for proper keratinocyte function and skin development
PLOS ONE, 2010Co-Authors: Aniruddha Sengupta, Bradley A. Carlson, Vadim N. Gladyshev, Ulrike Lichti, Andrew Ryscavage, Stuart H Yuspa, Dolph L HatfieldAbstract:Dietary selenium is known to protect skin against UV-induced damage and cancer and its topical application improves skin surface parameters in humans, while selenium deficiency compromises protective antioxidant enzymes in skin. Furthermore, skin and hair abnormalities in humans and rodents may be caused by selenium deficiency, which are overcome by dietary selenium supplementation. Most important biological functions of selenium are attributed to Selenoproteins, proteins containing selenium in the form of the amino acid, selenocysteine (Sec). Sec insertion into proteins depends on Sec tRNA; thus, knocking out the Sec tRNA gene (Trsp) ablates selenoprotein expression. We generated mice with targeted removal of Selenoproteins in keratin 14 (K14) expressing cells and their differentiated descendents. The knockout progeny had a runt phenotype, developed skin abnormalities and experienced premature death. Lack of Selenoproteins in epidermal cells led to the development of hyperplastic epidermis and aberrant hair follicle morphogenesis, accompanied by progressive alopecia after birth. Further analyses revealed that Selenoproteins are essential antioxidants in skin and unveiled their role in keratinocyte growth and viability. This study links severe selenoprotein deficiency to abnormalities in skin and hair and provides genetic evidence for the role of these proteins in keratinocyte function and cutaneous development.
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Selenoprotein T deficiency alters cell adhesion and elevates selenoprotein W expression in murine fibroblast cells
Biochemistry and Cell Biology, 2009Co-Authors: Aniruddha Sengupta, Vyacheslav M. Labunskyy, Bradley A. Carlson, Vadim N. Gladyshev, Dolph L HatfieldAbstract:Mammalian Selenoproteins have diverse functions, cellular locations, and evolutionary histories, but all use the amino acid selenocysteine (Sec), often present in the enzyme’s active site. Only about half of mammalian Selenoproteins have been functionally characterized, with most being oxidoreductases. The cellular role of selenoprotein T (SelT), manifesting a CxxU motif in a thioredoxin-like fold and localized to Golgi and the endoplasmic reticulum, is not known. To examine its biological function, we knocked down SelT expression in mouse fibroblast cells and found that SelT deficiency alters cell adhesion and enhances the expression of several oxidoreductase genes, while decreasing the expression of genes involved in cell structure organization, suggesting the involvement of SelT in redox regulation and cell anchorage. Furthermore, we found that the loss of SelT elevates expression of another selenoprotein, selenoprotein W (SepW1). SelT and SepW1 belong to the same protein family, suggesting that SepW1 ...
Elias S J Arner - One of the best experts on this subject based on the ideXlab platform.
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Overexpression of Recombinant Selenoproteins in E. coli
Methods of Molecular Biology, 2017Co-Authors: Qing Cheng, Elias S J ArnerAbstract:Expression of Selenoproteins necessitates a process of decoding of a UGA codon from termination of translation to insertion of selenocysteine. The mechanisms of this process pose major challenges with regards to recombinant selenoprotein production in E. coli, which however can be overcome especially if the Sec residue is located close to the C-terminal end, as is the case for several naturally found Selenoproteins. This chapter summarizes a method to achieve such a production.
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selenocysteine insertion at a predefined uag codon in a release factor 1 rf1 depleted escherichia coli host strain bypasses species barriers in recombinant selenoprotein translation
Journal of Biological Chemistry, 2017Co-Authors: Qing Cheng, Elias S J ArnerAbstract:Abstract Selenoproteins contain the amino acid selenocysteine (Sec), co-translationally inserted at a predefined UGA opal codon by means of Sec-specific translation machineries. In Escherichia coli, this process is dependent upon binding of the Sec-dedicated elongation factor SelB to a Sec insertion sequence (SECIS) element in the selenoprotein-encoding mRNA and competes with UGA-directed translational termination. Here, we found that Sec can also be efficiently incorporated at a predefined UAG amber codon, thereby competing with RF1 rather than RF2. Subsequently, utilizing the RF1-depleted E. coli strain C321.ΔA, we could produce mammalian selenoprotein thioredoxin reductases with unsurpassed purity and yield. We also found that a SECIS element was no longer absolutely required in such a system. Human glutathione peroxidase 1 could thereby also be produced, and we could confirm a previously proposed catalytic tetrad in this selenoprotein. We believe that the versatility of this new UAG-directed production methodology should enable many further studies of diverse Selenoproteins.
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selenoprotein gene nomenclature
Journal of Biological Chemistry, 2016Co-Authors: Raymond F. Burk, Brigelius Flohe Regina, Sergi Castellano, Elspeth A Bruford, Elias S J Arner, Bradley A. Carlson, Vadim N. Gladyshev, Marla J Berry, Laurent ChavatteAbstract:Abstract The human genome contains 25 genes coding for selenocysteine-containing proteins (Selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to Selenoproteins across vertebrates.
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selenoprotein gene nomenclature
Journal of Biological Chemistry, 2016Co-Authors: Raymond F. Burk, Brigelius Flohe Regina, Sergi Castellano, Elspeth A Bruford, Elias S J Arner, Bradley A. Carlson, Vadim N. Gladyshev, Marla J Berry, Laurent ChavatteAbstract:Abstract The human genome contains 25 genes coding for selenocysteine-containing proteins (Selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to Selenoproteins across vertebrates.
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Selenoproteins what unique properties can arise with selenocysteine in place of cysteine
Experimental Cell Research, 2010Co-Authors: Elias S J ArnerAbstract:The defining entity of a selenoprotein is the inclusion of at least one selenocysteine (Sec) residue in its sequence. Sec, the 21st naturally occurring genetically encoded amino acid, differs from its significantly more common structural analog cysteine (Cys) by the identity of a single atom: Sec contains selenium instead of the sulfur found in Cys. Selenium clearly has unique chemical properties that differ from sulfur, but more striking are perhaps the similarities between the two elements. Selenium was discovered by Jons Jacob Berzelius, a renowned Swedish scientist instrumental in establishing the institution that would become Karolinska Institutet. Written at the occasion of the bicentennial anniversary of Karolinska Institutet, this mini review focuses on the unique selenium-derived properties that may potentially arise in a protein upon the inclusion of Sec in place of Cys. With 25 human genes encoding Selenoproteins and in total several thousand Selenoproteins yet described in nature, it seems likely that the presence of that single selenium atom of Sec should convey some specific feature, thereby explaining the existence of Selenoproteins in spite of demanding and energetically costly Sec-specific synthesis machineries. Nonetheless, most, if not all, of the currently known Selenoproteins are also found as Cys-containing non-selenoprotein orthologues in other organisms, wherefore any potentially unique properties of Selenoproteins are yet a matter of debate. The pKa of free Sec (approximately 5.2) being significantly lower than that of free Cys (approximately 8.5) has often been proposed as one of the unique features of Sec. However, as discussed herein, this pKa difference between Sec and Cys can hardly provide an evolutionary pressure for maintenance of Selenoproteins. Moreover, the typically 10- to 100-fold lower enzymatic efficiencies of Sec-to-Cys mutants of selenoprotein oxidoreductases, are also weak arguments for the overall existence of Selenoproteins. Here, it is however emphasized that the inherent high nucleophilicity of Sec and thereby its higher chemical reaction rate with electrophiles, as compared to Cys, seems to be a truly unique property of Sec that cannot easily be mimicked by the basicity of Cys, even within the microenvironment of a protein. The chemical rate enhancement obtained with Sec can have other consequences than those arising from a low redox potential of some Cys-dependent proteins, typically aiming at maintaining redox equilibria. Another unique aspect of Sec compared to Cys seems to be its efficient potency to support one-electron transfer reactions, which, however, has not yet been unequivocally shown as a Sec-dependent step during the natural catalysis of any known selenoprotein enzyme.
Laurent Chavatte - One of the best experts on this subject based on the ideXlab platform.
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selenoprotein gene nomenclature
Journal of Biological Chemistry, 2016Co-Authors: Raymond F. Burk, Brigelius Flohe Regina, Sergi Castellano, Elspeth A Bruford, Elias S J Arner, Bradley A. Carlson, Vadim N. Gladyshev, Marla J Berry, Laurent ChavatteAbstract:Abstract The human genome contains 25 genes coding for selenocysteine-containing proteins (Selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to Selenoproteins across vertebrates.
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selenoprotein gene nomenclature
Journal of Biological Chemistry, 2016Co-Authors: Raymond F. Burk, Brigelius Flohe Regina, Sergi Castellano, Elspeth A Bruford, Elias S J Arner, Bradley A. Carlson, Vadim N. Gladyshev, Marla J Berry, Laurent ChavatteAbstract:Abstract The human genome contains 25 genes coding for selenocysteine-containing proteins (Selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to Selenoproteins across vertebrates.
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selective up regulation of human Selenoproteins in response to oxidative stress
Journal of Biological Chemistry, 2014Co-Authors: Zahia Touathamici, Yona Legrain, Annelaure Bulteau, Laurent ChavatteAbstract:Selenocysteine is inserted into Selenoproteins via the translational recoding of a UGA codon, normally used as a stop signal. This process depends on the nature of the selenocysteine insertion sequence element located in the 3′ UTR of selenoprotein mRNAs, selenium bioavailability, and, possibly, exogenous stimuli. To further understand the function and regulation of Selenoproteins in antioxidant defense and redox homeostasis, we investigated how oxidative stress influences selenoprotein expression as a function of different selenium concentrations. We found that selenium supplementation of the culture media, which resulted in a hierarchical up-regulation of Selenoproteins, protected HEK293 cells from reactive oxygen species formation. Furthermore, in response to oxidative stress, we identified a selective up-regulation of several Selenoproteins involved in antioxidant defense (Gpx1, Gpx4, TR1, SelS, SelK, and Sps2). Interestingly, the response was more efficient when selenium was limiting. Although a modest change in mRNA levels was noted, we identified a novel translational control mechanism stimulated by oxidative stress that is characterized by up-regulation of UGA-selenocysteine recoding efficiency and relocalization of SBP2, selenocysteine-specific elongation factor, and L30 recoding factors from the cytoplasm to the nucleus.
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Speciation analysis for trace levels of Selenoproteins in cultured human cells
J. Proteomics, 2014Co-Authors: J. Bianga, Laurent Chavatte, Z. Touat-hamici, Katarzyna Bierla, Sandra Mounicou, Joanna Szpunar, Ryszard LobinskiAbstract:A semi-quantitative method was developed for the non-targeted detection of trace levels of human Selenoproteins in cytoplasmic cell extracts without the use of radioactive isotopes. The method was based on the direct detection of Selenoproteins in iso-electrofocusing (IEF) electrophoretic strips by laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS). The proteins were identified in the non-ablated parts of the gel corresponding to the LA-ICP MS peak apexes by electrospray Orbitrap MS/MS. The method allowed a high resolution of the Selenoproteins (peak width 0.06pH unit) using 3-10 pI strips. The protein detection limits were down to 1ngmL-1 (as Se). The method was applied to the selenoprotein speciation in different human cell lines: Hek293 (kidney), HepG2 (liver), HaCaT (skin) and LNCaP (prostate). The principal proteins found included Selenoprotein 15 (Sep15), Glutathione peroxidase 1 (GPx1) and Glutathione peroxidase 4 (GPx4) and Thioredoxin reductase 1 (TRxR1) and Thioredoxin reductase 2 (TRxR2). Biological significance: Our paper presents the development of a semi-quantitative method for the non-targeted detection of trace levels of human Selenoproteins in cytoplasmic cell extracts; it offers a first comprehensive screening of the entire biological selenoproteomes expressed in cell lines without the use of radioactive 75Se. The method was based on the direct detection of Selenoproteins in iso-electrofocusing (IEF) electrophoretic strips by laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS). The proteins were identified in the non-ablated parts of the gel corresponding to the LA-ICP MS peak apexes by electrospray Orbitrap MS/MS. The method allowed a high resolution of the Selenoproteins (peak width 0.06pH unit) using 3-10 pI strips. The protein detection limits were down to 1ngmL-1 (as Se); by far the lowest ever reported. The method was applied to the selenoprotein speciation in different human cell lines: Hek293 (kidney), HepG2 (liver), HaCaT (skin) and LNCaP (prostate). The principal proteins found included Selenoprotein 15 (Sep15), Glutathione peroxidase 1 (GPx1) and Glutathione peroxidase 4 (GPx4) and Thioredoxin reductase 1 (TRxR1) and Thioredoxin reductase 2 (TRxR2). The IEF-LA-ICPMS indicates the presence of multiple forms of some Selenoproteins which are for the moment impossible to distinguish because of the similarity of the bottom-up, proteomics data sets.
