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Human mitochondrial thioredoxin reductase: cDNA cloning, expression and genomic organization
Abstract
We have isolated a 1918‐bp cDNA from a human adrenal cDNA library which encodes a novel thioredoxin reductase (TrxR2) of 521 amino acid residues with a calculated molecular mass of 56.2 kDa. It is highly homologous to the previously described cytosolic enzyme (TrxR1), including the conserved active site CVNVGC and the FAD‐binding and NADPH‐binding domains. However, human TrxR2 differs from human TrxR1 by the presence of a 33‐amino acid extension at the N‐terminus which has properties characteristic of a mitochondrial translocation signal. Northern‐blot analysis identified one mRNA species of 2.2 kb with highest expression in prostate, testis and liver. We expressed human TrxR2 as a fusion protein with green fluorescent protein and showed that in vivo it is localized in mitochondria. Removal of the mitochondrial targeting sequence abolishes the mitochondrial translocation. Finally, we determined the genomic organization of the human TrxR2 gene, which consists of 18 exons spanning about 67 kb, and its chromosomal localization at position 22q11.2.
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Cites
Keilin's Respiratory Chain Concept and Its Chemiosmotic Consequences
Mitchell, P. (1979) · Science · doi:10.1126/science.388618 · Cited by 738
Cited by
Thioredoxin and Related Molecules–From Biology to Health and Disease
Lillig, C. H., & Holmgren, A. (2007) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.9.25 · Cited by 724
PGC-1α regulates the mitochondrial antioxidant defense system in vascular endothelial cells
VALLE, I., ALVAREZBARRIENTOS, A., ARZA, E., LAMAS, S., & MONSALVE, M. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.01.026 · Cited by 556
Zhong, L., Arnér, E. S. J., & Holmgren, A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.100114897 · Cited by 527
Targeting the Thioredoxin System for Cancer Therapy
Zhang, J., Li, X., Han, X., Liu, R., & Fang, J. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.06.001 · Cited by 460
On the potential of thioredoxin reductase inhibitors for cancer therapy
Urig, S., & Becker, K. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.09.004 · Cited by 337
Metadata
- Authors
- Miranda‐Vizuete, A., Damdimopoulos, A. E., Pedrajas, J. R., Gustafsson, J., & Spyrou, G.
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 1999-04
- Volume
- 261
- Issue
- 2
- Pages
- 405-412
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W1574486032
- Cited by
- 178
- References
- 1
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- closed
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- Miranda‐Vizuete, A., Damdimopoulos, A. E., Pedrajas, J. R., Gustafsson, J., & Spyrou, G. (1999). Human mitochondrial thioredoxin reductase: cDNA cloning, expression and genomic organization. European Journal of Biochemistry. https://doi.org/10.1046/j.1432-1327.1999.00286.x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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