Redox Regulation of Cell Signaling by Thioredoxin Reductases

Sun, Qi; Gladyshev, Vadim N.

doi:10.1016/s0076-6879(02)47045-0

Cited by 12 publications

(10 citation statements)

References 16 publications

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“…TR1 and TR3 were affinity purified on 2′,5′-ADP-Sepharose columns, the purified proteins reduced with DTT, followed by alkylation of the Cys and Sec residues with iodoacetamide as described in detail elsewhere (27,28). Alkylated proteins were resolved by SDS-PAGE using Novex NU-PAGE system (Invitrogen) and stained with Coomassie blue.…”

Section: Methodsmentioning

confidence: 99%

Targeted insertion of cysteine by decoding UGA codons with mammalian selenocysteine machinery

Turanov

Carlson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Cysteine (Cys) is inserted into proteins in response to UGC and UGU codons. Herein, we show that supplementation of mammalian cells with thiophosphate led to targeted insertion of Cys at the UGA codon of thioredoxin reductase 1 (TR1). This Cys was synthesized by selenocysteine (Sec) synthase on tRNA ½SerSec and its insertion was dependent on the Sec insertion sequence element in the 3′ UTR of TR1 mRNA. The substrate for this reaction, thiophosphate, was synthesized by selenophosphate synthetase 2 from ATP and sulfide and reacted with phosphoseryl-tRNA ½SerSec to generate Cys-tRNA ½SerSec . Cys was inserted in vivo at UGA codons in natural mammalian TRs, and this process was regulated by dietary selenium and availability of thiophosphate. Cys occurred at 10% of the Sec levels in liver TR1 of mice maintained on a diet with normal amounts of selenium and at 50% in liver TR1 of mice maintained on a selenium deficient diet. These data reveal a novel Sec machinerybased mechanism for biosynthesis and insertion of Cys into protein at UGA codons and suggest new biological functions for thiophosphate and sulfide in mammals.de novo synthesis | new biosynthetic pathway | selenium deficiency

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Section: Methodsmentioning

confidence: 99%

Targeted insertion of cysteine by decoding UGA codons with mammalian selenocysteine machinery

Turanov

Carlson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Isolation of Proteins-Mouse and rat TR1 and TGR were isolated from liver and testes using a three-step procedure (8,18). The fragment encoding the Grx domain of mouse TGR was amplified with primers 5Ј-GAGATTCCATATGGCGTCGCCACCCGGCCGCCG-3Ј and 5Ј-CG-GAATTCTTAGTCATCTTGAAGGAGCTTCTGCA-3Ј and cloned into pET28a (Novagen).…”

Section: Methodsmentioning

confidence: 99%

Mammalian Selenoprotein Thioredoxin-glutathione Reductase

Su¹,

Novoselov²,

Sun³

et al. 2005

Journal of Biological Chemistry

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170

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Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium in male reproduction.

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“…Among the signaling proteins (and their critical cysteines) that have been well characterized are the PTPs, PTP1B (cys 215 ) (26,27,(34)(35)(36), low molecular weight PTP (cys12,17) (37-39) and Srchomology 2 domain-containing PTP (SHP-2) (40), the small G protein, Ras (cys 118 ) (41)(42)(43)(44), the large G proteins, G i (cys 267 ) and G o (cys 326 ) (45) and the lipid phosphatase, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). In addition, as mentioned above, in its reduced form Trx binds and inhibits ASK1 and possibly other signaling proteins as well (46)(47)(48)(49)(50)(51)(52)(53). When oxidized by formation of a disulfide between the two cysteines in its active site, Trx dissociates from ASK1, allowing it to become activated (46)(47)(48)(49)(50)(51)(52)(53) (Figure 1).…”

Section: A Signaling Proteins In Which Critical Cysteines Are Modifiedmentioning

confidence: 99%

“…In addition, as mentioned above, in its reduced form Trx binds and inhibits ASK1 and possibly other signaling proteins as well (46)(47)(48)(49)(50)(51)(52)(53). When oxidized by formation of a disulfide between the two cysteines in its active site, Trx dissociates from ASK1, allowing it to become activated (46)(47)(48)(49)(50)(51)(52)(53) (Figure 1). Also, GSTΠ inhibits c-Jun-N-terminal kinase (JNK) but dissociates and allows JNK activation when its critical active site cysteine is oxidized (54)(55)(56).…”

Section: A Signaling Proteins In Which Critical Cysteines Are Modifiedmentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

217

160

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During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H 2 O 2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. Keywords signaling; glutathione; thioredoxin; oxidants; reactive oxygen species; thiols; peroxide; nitric oxide; peroxynitrite; 4-hydroxynonenal; cysteine; hydrogen peroxide; protein tyrosine phosphatase; reactive nitrogen species; eNOS; iNOS; nNOS; soluble guanylate cyclase; cGMP; tyrosine nitration; fatty acid nitration; NO-heme; NO-metal complexes; nitrite; protein kinase C; ERK; JNK; p38MAPK; tyrosine kinase receptors; calcium OVERVIEW OF SIGNALING BY REACTIVE SPECIESUnderstanding of the roles of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE) in signaling has evolved rapidly during the last decade. This has been markedly helped by identification of the specific targets in signaling pathways. In previous reviews, we defined how ROS, H 2 O 2 in particular,

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Redox Regulation of Cell Signaling by Thioredoxin Reductases

Cited by 12 publications

References 16 publications

Targeted insertion of cysteine by decoding UGA codons with mammalian selenocysteine machinery

Targeted insertion of cysteine by decoding UGA codons with mammalian selenocysteine machinery

Mammalian Selenoprotein Thioredoxin-glutathione Reductase

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

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