Thioredoxin-related protein 14, a new member of the thioredoxin family with disulfide reductase activity: Implication in the redox regulation of TNF-α signaling

Jeong, Woojin; Jung, Yoon Young; Kim, Hojin; Park, Sun Joo; Rhee, Sue Goo

doi:10.1016/j.freeradbiomed.2009.07.021

Cited by 42 publications

(40 citation statements)

References 117 publications

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“…The most prominent and ubiquitously expressed components of the Trx system are the cytosolic TrxR1 (encoded by the Txnrd1 gene) and its main substrate Trx1 (34,35). Another less characterized substrate of TrxR1 is TRP14 (36), discovered as a TrxR1-dependent oxidoreductase affecting TNF-α-induced NF-κB activation, which displays a more restricted substrate specificity than Trx1 (37,38).…”

mentioning

confidence: 99%

Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-β receptor tyrosine kinase signaling

Dagnell

Frijhoff

Pader

et al. 2013

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

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The inhibitory reversible oxidation of protein tyrosine phosphatases (PTPs) is an important regulatory mechanism in growth factor signaling. Studies on PTP oxidation have focused on pathways that increase or decrease reactive oxygen species levels and thereby affect PTP oxidation. The processes involved in reactivation of oxidized PTPs remain largely unknown. Here the role of the thioredoxin (Trx) system in reactivation of oxidized PTPs was analyzed using a combination of in vitro and cell-based assays. Cells lacking the major Trx reductase TrxR1 (Txnrd1 −/− ) displayed increased oxidation of PTP1B, whereas SHP2 oxidation was unchanged. Furthermore, in vivo-oxidized PTP1B was reduced by exogenously added Trx system components, whereas SHP2 oxidation remained unchanged. Trx1 reduced oxidized PTP1B in vitro but failed to reactivate oxidized SHP2. Interestingly, the alternative TrxR1 substrate TRP14 also reactivated oxidized PTP1B, but not SHP2. Txnrd1-depleted cells displayed increased phosphorylation of PDGF-β receptor, and an enhanced mitogenic response, after PDGF-BB stimulation. The TrxR inhibitor auranofin also increased PDGF-β receptor phosphorylation. This effect was not observed in cells specifically lacking PTP1B. Together these results demonstrate that the Trx system, including both Trx1 and TRP14, impacts differentially on the oxidation of individual PTPs, with a preference of PTP1B over SHP2 activation. The studies demonstrate a previously unrecognized pathway for selective redox-regulated control of receptor tyrosine kinase signaling.redox regulation | cell signaling

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mentioning

confidence: 99%

Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-β receptor tyrosine kinase signaling

Dagnell

Frijhoff

Pader

et al. 2013

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

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“…Shutting-off NF-jB signaling thus activated appears to be clarified. Oxidized TRP14 is reduced by the cytosolic form of Trx reductase TrxR1, but not by the mitochondrial TrxR2 (222,224). Remains the questions how the activating oxidation of LC8 is achieved.…”

Section: Brigelius-flohé and Flohémentioning

confidence: 99%

“…The oxidation is reversed by the Trx homolog thioredoxin-related protein-14 (TRP14), which is reduced by cytosolic thioredoxin reductase (TrxR1). In this system either LC9 itself is the sensor or is oxidized by an upstream sensing thiol peroxidase (224).…”

Section: Sensing and Transducing Proteinsmentioning

confidence: 99%

“…By maintaining LC8 in the reduced state, TRP14 prevents cytosolic activation of NF-jB. Exposure to oxidants or treatment with TNFa, IL-1, or LPS known to signal via H 2 O 2 production leads to the formation of LC8 dimers in which two molecules are linked via a disulfide bridge (515), resulting in its dissociation from IjB (224,227). This mode of redox-dependent inhibition of protein activities by interaction with binding partners is analogous to the association of Trx to ASK-1, an upstream activator of the c-Jun N-terminal kinase (INK) and p-38 MAPK signaling pathways (415) (Fig.…”

Section: Brigelius-flohé and Flohémentioning

confidence: 99%

“…TRP14 having a redox potential ( -257 mV) (222) between those of Trxs and Grxs might be able to catalyze thiol/disulfide exchange both ways and thus might be the ROOH acceptor that oxidizes LC8, but the reaction of TRP14 with H 2 O 2 is reportedly just four times as fast as that of Trx, which has been rated as disappointingly slow (224). The possibility that TRP14, in analogy to other redoxins, might be oxidized by an ROOHsensing Prx has evidently been ruled out experimentally (224). We are thus left with the options that LC8 itself has the capacity to sense ROOH or is oxidized by a still unknown upstream redox sensor.…”

Section: Brigelius-flohé and Flohémentioning

confidence: 99%

See 2 more Smart Citations

Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors

Brigelius‐Flohé

Flohé

2011

Antioxidants & Redox Signaling

513

442

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Convincing concepts of redox control of gene transcription have been worked out for prokaryotes and lower eukaryotes, whereas the knowledge on complex mammalian systems still resembles a patchwork of poorly connected findings. The article, therefore, reviews principles of redox regulation with special emphasis on chemical feasibility, kinetic requirements, specificity, and physiological context, taking well investigated mammalian transcription factor systems, nuclear transcription factor of bone marrow-derived lymphocytes (NFjB), and kelch-like ECH-associated protein-1 (Keap1)/Nrf2, as paradigms. Major conclusions are that (i) direct signaling by free radicals is restricted to O 2 -and NO and can be excluded for fast reacting radicals such as OH, OR, or Cl ; (ii) oxidant signals are H 2 O 2 , enzymatically generated lipid hydroperoxides, and peroxynitrite; (iii) free radical damage is sensed via generation of Michael acceptors; (iv) protein thiol oxidation/alkylation is the prominent mechanism to modulate function; (v) redox sensors must be thiol peroxidases by themselves or proteins with similarly reactive cysteine or selenocysteine (Sec) residues to kinetically compete with glutathione peroxidase (GPx)-and peroxiredoxin (Prx)-type peroxidases or glutathione-S-transferases, respectively, a postulate that still has to be verified for putative mammalian sensors. S-transferases and Prxs are considered for system complementation. The impact of NF-jB and Nrf2 on hormesis, management of inflammatory diseases, and cancer prevention is critically discussed. Antioxid. Redox Signal. 15, 2335-2381.

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Structure‐based analysis of Clot as a thioredoxin‐related protein of 14 kDa in Drosophila via experimental and computational approaches

Kim

2017

Biotech and App Biochem

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The clot gene is required for the biosynthesis of drosopterins, the red components of Drosophila eye pigments. However, the enzymatic role of Clot in Drosophila eye pigment formation and the molecular mechanisms underlying Clot function are not fully elucidated. In this study, we cloned and characterized Clot derived from Drosophila cDNA, and results showed that Clot exhibited ∼30% sequence identity with mammalian TRP14. In addition, we reported the three-dimensional structure of Drosophila Clot based on homology modeling. Furthermore, we identified NFκB as a novel Clot substrate using the I-TASSER program. The NFκB fragment can bind near the active site of Clot. These findings predicted the novel regulatory mechanisms underlying Clot function in the pyrimidodiazepine synthesis pathway and increased the understanding of the molecular mechanisms and physiological function of Clot in Drosophila eye pigment formation.

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Thioredoxin-related protein 14, a new member of the thioredoxin family with disulfide reductase activity: Implication in the redox regulation of TNF-α signaling

Cited by 42 publications

References 117 publications

Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-β receptor tyrosine kinase signaling

Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-β receptor tyrosine kinase signaling

Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors

Structure‐based analysis of Clot as a thioredoxin‐related protein of 14 kDa in Drosophila via experimental and computational approaches

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