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TXN2  -  thioredoxin 2

Homo sapiens

Synonyms: MT-TRX, MTRX, Mt-Trx, TRX2, Thioredoxin, mitochondrial, ...
 
 
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Disease relevance of TXN2

  • The active site motif of TXN2, 40WCPPCR45, of Crithidia fasciculata was mutated by site-directed mutagenesis and eight corresponding muteins were expressed in E. coli as terminally His-tagged proteins, purified to homogeneity by nickel chelate chromatography, and characterized in terms of specific activity, specificity and, if possible, kinetics [1].
  • Thiol-related genes in diabetic complications: a novel protective role for endogenous thioredoxin 2 [2].
  • Helicobacter pylori possesses two distinct thioredoxin proteins (Trx1 and Trx2) which may play important roles in the ability of this bacterium to survive oxidative stress [3].
  • MitoQ, a mitochondria specific antioxidant, reversed HIF-1alpha accumulation as well as Akt activation under hypoxia in Trx2 cells, supporting the notion of translation control mechanisms in affecting HIF-1alpha protein accumulation [4].
 

High impact information on TXN2

 

Biological context of TXN2

  • Mitochondrial thioredoxin-2 has a key role in determining tumor necrosis factor-alpha-induced reactive oxygen species generation, NF-kappaB activation, and apoptosis [7].
  • Results showed that nuclear translocation of NF-kappaB was inhibited with Trx2 overexpression but not with the dominant negative active-site mutant C93S Trx2 [7].
  • Treatment with oligomycin could both reverse the effect of rotenone and decrease the membrane potential suggesting that Trx2 interferes with the activity of ATP synthase [6].
  • More detailed analysis showed that a number of mRNAs encoding proteins associated with the induction of oxidative stress, including thioredoxin-2 and thioredoxin-interacting protein were rapidly redistributed onto heavier polysomes at high glucose concentration, indicating an increase in their expression [8].
  • In spite of the absence of the Cys residue implicated in dimer formation in human thioredoxin 1, dimerization still occurs in the crystal structure of human thioredoxin 2, mainly mediated by hydrophobic contacts, and the dimers are associated to form two-dimensional polymers [9].
 

Anatomical context of TXN2

 

Associations of TXN2 with chemical compounds

 

Regulatory relationships of TXN2

  • These findings support the interpretation that mitochondrial-generated ROS is a principal component in TNF-alpha-induced effects and that Trx2 blocks TNF-alpha-induced ROS generation and downstream NF-kappaB activation and apoptosis [7].
  • Thioredoxin-2 inhibits mitochondria-located ASK1-mediated apoptosis in a JNK-independent manner [14].
 

Other interactions of TXN2

 

Analytical, diagnostic and therapeutic context of TXN2

References

  1. Permutation of the active site motif of tryparedoxin 2. Steinert, P., Plank-Schumacher, K., Montemartini, M., Hecht, H.J., Flohé, L. Biol. Chem. (2000) [Pubmed]
  2. Thiol-related genes in diabetic complications: a novel protective role for endogenous thioredoxin 2. Liang, M., Pietrusz, J.L. Arterioscler. Thromb. Vasc. Biol. (2007) [Pubmed]
  3. Role of the thioredoxin system and the thiol-peroxidases Tpx and Bcp in mediating resistance to oxidative and nitrosative stress in Helicobacter pylori. Comtois, S.L., Gidley, M.D., Kelly, D.J. Microbiology (Reading, Engl.) (2003) [Pubmed]
  4. Thioredoxin 1 and thioredoxin 2 have opposed regulatory functions on hypoxia-inducible factor-1alpha. Zhou, J., Damdimopoulos, A.E., Spyrou, G., Brüne, B. J. Biol. Chem. (2007) [Pubmed]
  5. Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis. Tanaka, T., Hosoi, F., Yamaguchi-Iwai, Y., Nakamura, H., Masutani, H., Ueda, S., Nishiyama, A., Takeda, S., Wada, H., Spyrou, G., Yodoi, J. EMBO J. (2002) [Pubmed]
  6. Human mitochondrial thioredoxin. Involvement in mitochondrial membrane potential and cell death. Damdimopoulos, A.E., Miranda-Vizuete, A., Pelto-Huikko, M., Gustafsson, J.A., Spyrou, G. J. Biol. Chem. (2002) [Pubmed]
  7. Mitochondrial thioredoxin-2 has a key role in determining tumor necrosis factor-alpha-induced reactive oxygen species generation, NF-kappaB activation, and apoptosis. Hansen, J.M., Zhang, H., Jones, D.P. Toxicol. Sci. (2006) [Pubmed]
  8. Distinct glucose-dependent stress responses revealed by translational profiling in pancreatic {beta}-cells. Greenman, I.C., Gomez, E., Moore, C.E., Herbert, T.P. J. Endocrinol. (2007) [Pubmed]
  9. Crystal structures of oxidized and reduced forms of human mitochondrial thioredoxin 2. Smeets, A., Evrard, C., Landtmeters, M., Marchand, C., Knoops, B., Declercq, J.P. Protein Sci. (2005) [Pubmed]
  10. The thioredoxin system in aging muscle: key role of mitochondrial thioredoxin reductase in the protective effects of caloric restriction? Rohrbach, S., Gruenler, S., Teschner, M., Holtz, J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  11. Evidence for an age-related attenuation of cerebral microvascular antioxidant response to oxidative stress. Williams, W.M., Chung, Y.W. Life Sci. (2006) [Pubmed]
  12. Differential oxidation of thioredoxin-1, thioredoxin-2, and glutathione by metal ions. Hansen, J.M., Zhang, H., Jones, D.P. Free Radic. Biol. Med. (2006) [Pubmed]
  13. Involvements of mitochondrial thioredoxin reductase (TrxR2) in cell proliferation. Kim, M.R., Chang, H.S., Kim, B.H., Kim, S., Baek, S.H., Kim, J.H., Lee, S.R., Kim, J.R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  14. Thioredoxin-2 inhibits mitochondria-located ASK1-mediated apoptosis in a JNK-independent manner. Zhang, R., Al-Lamki, R., Bai, L., Streb, J.W., Miano, J.M., Bradley, J., Min, W. Circ. Res. (2004) [Pubmed]
  15. Gene expression profiling reveals complex changes following MEK-EE expression in cardiac myocytes. Badrian, B., Bogoyevitch, M.A. Int. J. Biochem. Cell Biol. (2007) [Pubmed]
  16. Molecular and cellular characterization of imexon-resistant RPMI8226/I myeloma cells. Dvorakova, K., Payne, C.M., Tome, M.E., Briehl, M.M., Vasquez, M.A., Waltmire, C.N., Coon, A., Dorr, R.T. Mol. Cancer Ther. (2002) [Pubmed]
 
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