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Gene Review

TXNIP  -  thioredoxin interacting protein

Homo sapiens

Synonyms: EST01027, HHCPA78, THIF, Thioredoxin-binding protein 2, Thioredoxin-interacting protein, ...
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Disease relevance of TXNIP


High impact information on TXNIP


Chemical compound and disease context of TXNIP


Biological context of TXNIP


Anatomical context of TXNIP


Associations of TXNIP with chemical compounds

  • Reporter assays demonstrated that this glucocorticoid response element was necessary and sufficient for induction of txnip by dexamethasone [3].
  • PDGF and H2O2 time-dependently suppressed VDUP-1 expression (13-fold and 30-fold reduction after 1 hour, respectively; P<0.001), and this was inhibited by the cell-permeable antioxidants N-acetylcysteine and 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron) [18].
  • In contrast, incubation of INS-1 beta cells with equimolar amounts (25 mM) of l-glucose or mannitol had no effect on TXNIP expression as measured by real-time RT-PCR, eliminating the possibility of an osmotic effect [19].
  • We found that aside form glucose, the nonmetabolizable sugars 2-deoxyglucose, which is still converted to G-6-P as well as 3-O-methylglucose (3-MG), which cannot be phosphorylated by glucokinase, stimulate TXNIP expression [19].
  • Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated protein 1 (VDUP1), plays a crucial role in the integration of glucose and lipid metabolism [20].

Physical interactions of TXNIP

  • The deletion of HSE abolished transcriptional activity of VDUP1 promoter by stresses and the binding of heat shock factor (HSF) to HSE was confirmed by gel-shift and supershift assays using nuclear extracts prepared from stressed Bosc cells [21].
  • These cysteines are not conserved in the broader family of arrestin domain-containing proteins, and we demonstrate that the thioredoxin-binding property of Txnip is unique [7].

Regulatory relationships of TXNIP


Other interactions of TXNIP


Analytical, diagnostic and therapeutic context of TXNIP


  1. Melanoma metastasis suppression by chromosome 6: evidence for a pathway regulated by CRSP3 and TXNIP. Goldberg, S.F., Miele, M.E., Hatta, N., Takata, M., Paquette-Straub, C., Freedman, L.P., Welch, D.R. Cancer Res. (2003) [Pubmed]
  2. Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein. Schulze, P.C., Yoshioka, J., Takahashi, T., He, Z., King, G.L., Lee, R.T. J. Biol. Chem. (2004) [Pubmed]
  3. Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis. Wang, Z., Rong, Y.P., Malone, M.H., Davis, M.C., Zhong, F., Distelhorst, C.W. Oncogene (2006) [Pubmed]
  4. VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression. Han, S.H., Jeon, J.H., Ju, H.R., Jung, U., Kim, K.Y., Yoo, H.S., Lee, Y.H., Song, K.S., Hwang, H.M., Na, Y.S., Yang, Y., Lee, K.N., Choi, I. Oncogene (2003) [Pubmed]
  5. Fluid shear stress inhibits vascular inflammation by decreasing thioredoxin-interacting protein in endothelial cells. Yamawaki, H., Pan, S., Lee, R.T., Berk, B.C. J. Clin. Invest. (2005) [Pubmed]
  6. A Novel Role of Myosin VI in Human Prostate Cancer. Dunn, T.A., Chen, S., Faith, D.A., Hicks, J.L., Platz, E.A., Chen, Y., Ewing, C.M., Sauvageot, J., Isaacs, W.B., De Marzo, A.M., Luo, J. Am. J. Pathol. (2006) [Pubmed]
  7. The interaction of thioredoxin with Txnip. Evidence for formation of a mixed disulfide by disulfide exchange. Patwari, P., Higgins, L.J., Chutkow, W.A., Yoshioka, J., Lee, R.T. J. Biol. Chem. (2006) [Pubmed]
  8. Oxidative stress and thioredoxin-interacting protein promote intravasation of melanoma cells. Cheng, G.C., Schulze, P.C., Lee, R.T., Sylvan, J., Zetter, B.R., Huang, H. Exp. Cell Res. (2004) [Pubmed]
  9. Up-regulation of vitamin D3 up-regulated protein 1 gene in response to 5-fluorouracil in colon carcinoma SW620. Takahashi, Y., Nagata, T., Ishii, Y., Ikarashi, M., Ishikawa, K., Asai, S. Oncol. Rep. (2002) [Pubmed]
  10. Nitric oxide-dependent suppression of thioredoxin-interacting protein expression enhances thioredoxin activity. Schulze, P.C., Liu, H., Choe, E., Yoshioka, J., Shalev, A., Bloch, K.D., Lee, R.T. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  11. Vitamin D3 up-regulated protein 1 (VDUP1) expression in gastrointestinal cancer and its relation to stage of disease. Ikarashi, M., Takahashi, Y., Ishii, Y., Nagata, T., Asai, S., Ishikawa, K. Anticancer Res. (2002) [Pubmed]
  12. Hyperglycemia-induced thioredoxin-interacting protein expression differs in breast cancer-derived cells and regulates paclitaxel IC50. Turturro, F., Von Burton, G., Friday, E. Clin. Cancer Res. (2007) [Pubmed]
  13. Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis. Minn, A.H., Hafele, C., Shalev, A. Endocrinology (2005) [Pubmed]
  14. Localization of thioredoxin-interacting protein (TXNIP) mRNA in epithelium of human gastrointestinal tract. Takahashi, Y., Ishii, Y., Murata, A., Nagata, T., Asai, S. J. Histochem. Cytochem. (2003) [Pubmed]
  15. A central role for nicotinic cholinergic regulation of growth factor-induced endothelial cell migration. Ng, M.K., Wu, J., Chang, E., Wang, B.Y., Katzenberg-Clark, R., Ishii-Watabe, A., Cooke, J.P. Arterioscler. Thromb. Vasc. Biol. (2007) [Pubmed]
  16. An analysis of high glucose and glucosamine-induced gene expression and oxidative stress in renal mesangial cells. Cheng, D.W., Jiang, Y., Shalev, A., Kowluru, R., Crook, E.D., Singh, L.P. Arch. Physiol. Biochem. (2006) [Pubmed]
  17. The expression of vitamin D-upregulated protein 1 in skin and its interaction with sciellin in cultured keratinocytes. Champliaud, M.F., Viel, A., Baden, H.P. J. Invest. Dermatol. (2003) [Pubmed]
  18. Vitamin D3-upregulated protein-1 (VDUP-1) regulates redox-dependent vascular smooth muscle cell proliferation through interaction with thioredoxin. Schulze, P.C., De Keulenaer, G.W., Yoshioka, J., Kassik, K.A., Lee, R.T. Circ. Res. (2002) [Pubmed]
  19. Metabolism-independent sugar effects on gene transcription: the role of 3-o-methylglucose. Minn, A.H., Couto, F.M., Shalev, A. Biochemistry (2006) [Pubmed]
  20. Thioredoxin-binding protein-2-like inducible membrane protein is a novel vitamin D3 and peroxisome proliferator-activated receptor (PPAR)gamma ligand target protein that regulates PPARgamma signaling. Oka, S., Masutani, H., Liu, W., Horita, H., Wang, D., Kizaka-Kondoh, S., Yodoi, J. Endocrinology (2006) [Pubmed]
  21. Heat shock factor regulates VDUP1 gene expression. Kim, K.Y., Shin, S.M., Kim, J.K., Paik, S.G., Yang, Y., Choi, I. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  22. Role of thioredoxin in cell growth through interactions with signaling molecules. Yoshioka, J., Schreiter, E.R., Lee, R.T. Antioxid. Redox Signal. (2006) [Pubmed]
  23. Estradiol regulates the thioredoxin antioxidant system in the mouse uterus. Deroo, B.J., Hewitt, S.C., Peddada, S.D., Korach, K.S. Endocrinology (2004) [Pubmed]
  24. Identification of genes responsive to apoptosis in HL-60 cells. Jin, W., Qu, L.F., Min, P., Chen, S., Li, H., Lu, H., Hou, Y.T. Acta Pharmacol. Sin. (2004) [Pubmed]
  25. Isolation and characterization of a novel cDNA from HL-60 cells treated with 1,25-dihydroxyvitamin D-3. Chen, K.S., DeLuca, H.F. Biochim. Biophys. Acta (1994) [Pubmed]
  26. Exenatide inhibits beta-cell apoptosis by decreasing thioredoxin-interacting protein. Chen, J., Couto, F.M., Minn, A.H., Shalev, A. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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