The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

GABPA  -  GA binding protein transcription factor,...

Homo sapiens

Synonyms: E4TF1-60, E4TF1A, GA-binding protein alpha chain, GABP subunit alpha, NFT2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GABPA

  • Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: implication to tumor biology [1].
  • Taken together, this study suggests that identified antioxidant genes, which were upregulated through tBHQ induced Nrf2 stabilization, confer protection on target cells against H2O2-induced apoptotic cell death in neuroblastoma cells as well as the necrotic cell death in the hNSC [2].
  • In addition, a single polypeptide of 55 kDa was detected following cross-linking of a partially purified NRF-2 fraction to RCO4, the human ATP synthase beta subunit, or Moloney murine sarcoma virus binding sites [3].
  • When RBF-1 site was used for sequence specific DNA affinity purification from erythroleukemia cells, reconstitution assays, immunoblotting analysis and peptide mapping show that the two major co-purified proteins are identical to human E4TF1-60 and -53 proteins [4].
  • Although Nrf2 regulated these forms of neuronal toxicity, it was unclear which injury-triggered signal(s) led to Nrf2 activation in vivo [5].

Psychiatry related information on GABPA


High impact information on GABPA

  • However, upon recognition of chemical signals imparted by oxidative and electrophilic molecules, Nrf2 is released from Keap1, escapes proteasomal degradation, translocates to the nucleus, and transactivates the expression of several dozen cytoprotective genes that enhance cell survival [7].
  • The transcription factor Nrf2 has been implicated as the central protein that interacts with the ARE to activate gene transcription constitutively or in response to an oxidative stress signal [8].
  • This review focuses on the molecular mechanisms whereby the transcriptional activation mediated by the interaction between the ARE and NF-E2-related factor 2 (Nrf2) is regulated [8].
  • The Nrf2 peptide contains two short antiparallel beta-strands connected by two overlapping type I beta-turns stabilized by the aspartate and threonine residues [9].
  • Heterodimers of E4TF1-47 and E4TF1-60 weakly stimulated transcription in vitro [10].

Chemical compound and disease context of GABPA

  • Nrf2 knockout mice were more sensitive to kainate toxicity, as evidenced by elevated seizure severity, seizure duration, hippocampal neuron damage and mortality [11].

Biological context of GABPA

  • Mapping of the human transcription factor GABPA (E4TF1-60) gene to chromosome 21 [12].
  • One trapped sequence showed complete homology with nucleotide sequence D13318 of GenBank, which corresponds to the gene for human transcription factor E4TF1-60 (HGMW-approved nomenclature GABPA) [12].
  • The predicted amino acid sequence of each cDNA clone revealed that E4TF1-60 had an ETS domain, which is a DNA binding domain common to ets-related transcription factors [13].
  • A significant reduction of both steady-state and hypoxia/reoxygenation-mediated prx1 gene expression was shown in Nrf2 knock-out cells [1].
  • The results suggest that Nrf2-Keap1-dependent UGT1A1 induction by prooxidants might represent a key adaptive response to cellular oxidative stress that defends against a variety of environmental insults, including electrophile attacks and chemical carcinogenesis [14].

Anatomical context of GABPA


Associations of GABPA with chemical compounds

  • Gene mapping experiments including transfections of UGT1A1 reporter gene constructs into HepG2 cells coupled with functional analysis of Nrf2 expression and binding to anti-oxidant-response elements (ARE) resulted in identification of an ARE in the phenobarbital-response enhancer module region of the UGT1A1 gene [14].
  • Nrf2 stabilization by tBHQ also was observed in hNSCs [2].
  • Moreover, the 2- to 5-fold induction of these enzymes in wild-type mice by the chemoprotective agent oltipraz, which is currently in clinical trials, was almost completely abrogated in the nrf2-deficient mice [17].
  • NRF-2 binding and transcriptional activation required a purine-rich core sequence, GGAA [3].
  • These experiments provide a biochemical basis for the hypothesis that formation of J-ring compounds generated from oxidation of EPA and DHA in vivo can reach concentrations high enough to induce Nrf2-based cellular defense systems [18].

Other interactions of GABPA


Analytical, diagnostic and therapeutic context of GABPA


  1. Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: implication to tumor biology. Kim, Y.J., Ahn, J.Y., Liang, P., Ip, C., Zhang, Y., Park, Y.M. Cancer Res. (2007) [Pubmed]
  2. Stabilization of Nrf2 by tBHQ confers protection against oxidative stress-induced cell death in human neural stem cells. Li, J., Johnson, D., Calkins, M., Wright, L., Svendsen, C., Johnson, J. Toxicol. Sci. (2005) [Pubmed]
  3. Transcriptional activation through ETS domain binding sites in the cytochrome c oxidase subunit IV gene. Virbasius, J.V., Scarpulla, R.C. Mol. Cell. Biol. (1991) [Pubmed]
  4. The retinoblastoma binding factor 1 (RBF-1) site in RB gene promoter binds preferentially E4TF1, a member of the Ets transcription factors family. Savoysky, E., Mizuno, T., Sowa, Y., Watanabe, H., Sawada, J., Nomura, H., Ohsugi, Y., Handa, H., Sakai, T. Oncogene (1994) [Pubmed]
  5. Dopamine activates Nrf2-regulated neuroprotective pathways in astrocytes and meningeal cells. Shih, A.Y., Erb, H., Murphy, T.H. J. Neurochem. (2007) [Pubmed]
  6. Mechanistic studies of the nrf2-keap1 signaling pathway*. Zhang, D.D. Drug Metab. Rev. (2006) [Pubmed]
  7. Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway. Kensler, T.W., Wakabayashi, N., Biswal, S. Annu. Rev. Pharmacol. Toxicol. (2007) [Pubmed]
  8. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Nguyen, T., Sherratt, P.J., Pickett, C.B. Annu. Rev. Pharmacol. Toxicol. (2003) [Pubmed]
  9. Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling. Lo, S.C., Li, X., Henzl, M.T., Beamer, L.J., Hannink, M. EMBO J. (2006) [Pubmed]
  10. Transcriptional activation through the tetrameric complex formation of E4TF1 subunits. Sawada, J., Goto, M., Sawa, C., Watanabe, H., Handa, H. EMBO J. (1994) [Pubmed]
  11. Neuronal sensitivity to kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response element. Kraft, A.D., Lee, J.M., Johnson, D.A., Kan, Y.W., Johnson, J.A. J. Neurochem. (2006) [Pubmed]
  12. Mapping of the human transcription factor GABPA (E4TF1-60) gene to chromosome 21. Chrast, R., Chen, H., Morris, M.A., Antonarakis, S.E. Genomics (1995) [Pubmed]
  13. cDNA cloning of transcription factor E4TF1 subunits with Ets and notch motifs. Watanabe, H., Sawada, J., Yano, K., Yamaguchi, K., Goto, M., Handa, H. Mol. Cell. Biol. (1993) [Pubmed]
  14. Nrf2-Keap1 Signaling Pathway Regulates Human UGT1A1 Expression in Vitro and in Transgenic UGT1 Mice. Yueh, M.F., Tukey, R.H. J. Biol. Chem. (2007) [Pubmed]
  15. Induction of quinone reductase NQO1 by resveratrol in human K562 cells involves the antioxidant response element ARE and is accompanied by nuclear translocation of transcription factor Nrf2. Hsieh, T.C., Lu, X., Wang, Z., Wu, J.M. Medicinal chemistry (Sh⁻ariqah, United Arab Emirates) (2006) [Pubmed]
  16. NRF-2 transcription factor is essential in promoting human Tomm70 gene expression. Blesa, J.R., Hernández, J.M., Hernández-Yago, J. Mitochondrion (2004) [Pubmed]
  17. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Ramos-Gomez, M., Kwak, M.K., Dolan, P.M., Itoh, K., Yamamoto, M., Talalay, P., Kensler, T.W. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  18. Novel n-3 Fatty Acid Oxidation Products Activate Nrf2 by Destabilizing the Association between Keap1 and Cullin3. Gao, L., Wang, J., Sekhar, K.R., Yin, H., Yared, N.F., Schneider, S.N., Sasi, S., Dalton, T.P., Anderson, M.E., Chan, J.Y., Morrow, J.D., Freeman, M.L. J. Biol. Chem. (2007) [Pubmed]
  19. Cell-cycle-dependent regulation of human aurora A transcription is mediated by periodic repression of E4TF1. Tanaka, M., Ueda, A., Kanamori, H., Ideguchi, H., Yang, J., Kitajima, S., Ishigatsubo, Y. J. Biol. Chem. (2002) [Pubmed]
  20. Modulation of xenobiotic metabolising enzymes by anticarcinogens-focus on glutathione S-transferases and their role as targets of dietary chemoprevention in colorectal carcinogenesis. Pool-Zobel, B., Veeriah, S., Böhmer, F.D. Mutat. Res. (2005) [Pubmed]
  21. Structures, sequence characteristics, and synteny relationships of the transcription factor E4TF1, the splicing factor U2AF35 and the cystathionine beta synthetase genes from Fugu rubripes. Tassone, F., Villard, L., Clancy, K., Gardiner, K. Gene (1999) [Pubmed]
  22. Redox-sensitive interaction between KIAA0132 and Nrf2 mediates indomethacin-induced expression of gamma-glutamylcysteine synthetase. Sekhar, K.R., Spitz, D.R., Harris, S., Nguyen, T.T., Meredith, M.J., Holt, J.T., Gius, D., Marnett, L.J., Summar, M.L., Freeman, M.L., Guis, D. Free Radic. Biol. Med. (2002) [Pubmed]
  23. Glutathione Peroxidase 2, the Major Cigarette Smoke-Inducible Isoform of GPX in Lungs, Is Regulated by Nrf2. Singh, A., Rangasamy, T., Thimmulappa, R.K., Lee, H., Osburn, W.O., Brigelius-Floh??, R., Kensler, T.W., Yamamoto, M., Biswal, S. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  24. Nrf2 controls constitutive and inducible expression of ARE-driven genes through a dynamic pathway involving nucleocytoplasmic shuttling by Keap1. Nguyen, T., Sherratt, P.J., Nioi, P., Yang, C.S., Pickett, C.B. J. Biol. Chem. (2005) [Pubmed]
WikiGenes - Universities