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Title: An evolutionarily conserved 16-kDa thioredoxin-related protein is an antioxidant which regulates the NF-κB signaling pathway
Authors: Wang, X.W.
Liou, Y.-C. 
Ding, J.L. 
Ho, B. 
Keywords: Antioxidant
Free radicals
Horseshoe crab thioredoxin-related protein
Human thioredoxin
Innate immunity
Signal transduction
Issue Date: 2007
Citation: Wang, X.W., Liou, Y.-C., Ding, J.L., Ho, B. (2007). An evolutionarily conserved 16-kDa thioredoxin-related protein is an antioxidant which regulates the NF-κB signaling pathway. Free Radical Biology and Medicine 42 (2) : 247-259. ScholarBank@NUS Repository.
Abstract: Thioredoxin (TRX) is generally a 12-kDa protein-disulfide reductase. Here, we report the discovery of a 16-kDa thioredoxin-related protein designated Cr-TRP16, from a "living fossil," the horseshoe crab (Carcinoscorpius rotundicauda). Cr-TRP16 contains an atypical WCPPC catalytic motif and possesses the classical thiodisulfide reductase activity, as indicated by the insulin reduction assay. Furthermore, Cr-TRP16 can function as an antioxidant and protect against DNA nicking by reactive oxygen species. Overexpression of Cr-TRP16 regulated the transcription of NF-κB-dependent genes probably by enhancing NF-κB DNA-binding activity, suggesting possible roles for Cr-TRP16 in modulating the NF-κB signaling pathway. In vivo, the antioxidant pyrrolidine dithiocarbamate suppressed the expression of NF-κB-regulated genes such as IκB and inducible nitric oxide synthase. This further supports the notion that oxidative stress is also a regulatory factor of the NF-κB signaling pathway, a phenomenon which has been entrenched for several hundred million years. Furthermore, we demonstrated that the 16-kDa thioredoxins are evolutionarily conserved from Caenorhabditis elegans to human. Interestingly, thioredoxin-like 6, a human homologue of Cr-TRP16, could also enhance NF-κB DNA-binding activity, suggesting that the regulatory role of the 16-kDa thioredoxins on NF-κB is well conserved through evolution. © 2006 Elsevier Inc. All rights reserved.
Source Title: Free Radical Biology and Medicine
ISSN: 08915849
DOI: 10.1016/j.freeradbiomed.2006.10.040
Appears in Collections:Staff Publications

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