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Gene Review

GTF3A  -  general transcription factor IIIA

Homo sapiens

Synonyms: AP2, TFIIIA, Transcription factor IIIA
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Disease relevance of GTF3A

  • The role of invasion and metastasis-promoting MMPs and their potential regulators, AP-2 and HER2, is currently still unclear in breast cancer [1].
  • Loss of AP-2 results in up-regulation of MCAM/MUC18 and an increase in tumor growth and metastasis of human melanoma cells [2].
  • HER2-positivity was most often seen in carcinomas having both high nuclear and high cytoplasmic AP-2 expression (P < 0.001) [3].
  • Moreover, we demonstrated the interaction between endogenous AP-2 and YY1 factors in the BT-474 mammary adenocarcinoma cell line [4].
  • N-ras oncogene-induced transformation of human teratocarcinoma cells PA-1 results in sixfold elevated AP-2 mRNA levels [5].

High impact information on GTF3A

  • Acetylation of the N-terminal tails of the core histones directly facilitates the recognition by TFIIIA of the 5S RNA gene within model chromatin templates [6].
  • The nucleotide sequence of this conserved DNA on the human Y chromosome suggests that it encodes a protein with multiple "finger" domains, as first described in frog transcription factor IIIA [7].
  • The product of the first of these loci (factor A) is present in significant excess in normal fibroblasts, seems to turn over rapidly and may be a dimer or higher polymer [8].
  • This effect is specific for 5S RNA genes, since TFIIIA will not form an active template when incubated with a cloned Bombyx mori alanine tRNA gene [9].
  • The two 'zinc-finger'-like motifs fold to form a single structural domain and are thus distinct from the independently folded units of the TFIIIA-type zinc fingers [10].

Chemical compound and disease context of GTF3A


Biological context of GTF3A


Anatomical context of GTF3A

  • The 5S gene-specific transcription factor, TFIIIA, was purified approximately 35,000-fold from HeLa cell extracts using a combination of conventional and affinity chromatographic methods [19].
  • This region also contains elements that confer the capacity for activation by AP2, a transcription factor found to be expressed by corneal epithelial cells but not by corneal fibroblasts [20].
  • Levels of AP-2 and Sp1 proteins in a panel of melanoma cell lines demonstrated a marked decrease in the ratio of AP-2/Sp1, a decrease that correlated with overexpression of PAR-1 in metastatic melanoma cells [21].
  • We have now characterized immunological reagents that enable specific AP-2 family members, including AP-2alpha and AP-2gamma, to be detected in human breast cancer epithelium [22].
  • cDNA clones reveal differences between human glial and endothelial cell platelet-derived growth factor A-chains [23].

Associations of GTF3A with chemical compounds

  • In fact, AP-2 mRNA is repressed by both TPA and the calcium ionophore A23187 through a delayed response [24].
  • For example, after incubation with EDTA at room temperature, the patient's platelets bound little of the monoclonal antibodies AP-2 or T10 (anti-GP IIb-IIIa complex) although normally binding Tab (anti-GP IIb) [25].
  • The phenylalanine-based FQQI GLUT4 motif promotes AP-2-dependent internalization less rapidly than a tyrosine-based motif, the classic form of aromatic-based motifs [26].
  • A novel jasmonate- and elicitor-responsive element in the periwinkle secondary metabolite biosynthetic gene Str interacts with a jasmonate- and elicitor-inducible AP2-domain transcription factor, ORCA2 [27].
  • The remaining GLUT4 is internalized by an AP-2-dependent, nystatin-resistant pathway that requires the FQQI GLUT4 motif [26].

Physical interactions of GTF3A

  • In vitro interaction of recombinant human TFIIIA-intP with recombinant Xenopus TFIIIA was demonstrated by immuno-precipitation of the complex using anti-TFIIIA-intP antibody [17].
  • These results show that hTFIIIC binds to its promoter sequences in a metal coordinated fashion which differs from that observed for the binding of hTFIIIA to the 5S gene [28].
  • Transcription factor IIIC (TFIIIC) is a general RNA polymerase III transcription factor that binds the B-box internal promotor element of tRNA genes and the complex of TFIIIA with a 5S rRNA gene [29].
  • P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA [30].
  • NO-treated ECs resulted in a reduction of binding of nuclear proteins to the Egr-1 binding sequences in the platelet-derived growth factor-A promoter region [31].

Regulatory relationships of GTF3A


Other interactions of GTF3A

  • In contrast, restoration of 5S RNA gene transcription requires readdition of both TFIIIC and TFIIIA, indicating a promoter-independent interaction between these factors [36].
  • Among four distinct components required for accurate transcription in vitro from cloned DNA templates, activities of RNA polymerase III and transcription factor TFIIIA were not significantly affected by virus infection [37].
  • Carriage of multiple proinflammatory polymorphisms of IL-1B(o) IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes [38].
  • A role for PDGF-A chain in mediating intimal proliferation has been suggested in human atherosclerosis (Rekhter MD, Gordon D: Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques [39]?
  • Regulation of platelet-derived growth factor-A chain by Krüppel-like factor 5: new pathway of cooperative activation with nuclear factor-kappaB [40].

Analytical, diagnostic and therapeutic context of GTF3A


  1. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis. Pellikainen, J.M., Ropponen, K.M., Kataja, V.V., Kellokoski, J.K., Eskelinen, M.J., Kosma, V.M. Clin. Cancer Res. (2004) [Pubmed]
  2. Loss of AP-2 results in up-regulation of MCAM/MUC18 and an increase in tumor growth and metastasis of human melanoma cells. Jean, D., Gershenwald, J.E., Huang, S., Luca, M., Hudson, M.J., Tainsky, M.A., Bar-Eli, M. J. Biol. Chem. (1998) [Pubmed]
  3. Expression of HER2 and its association with AP-2 in breast cancer. Pellikainen, J., Naukkarinen, A., Ropponen, K., Rummukainen, J., Kataja, V., Kellokoski, J., Eskelinen, M., Kosma, V.M. Eur. J. Cancer (2004) [Pubmed]
  4. Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression in mammary cancer cells. Begon, D.Y., Delacroix, L., Vernimmen, D., Jackers, P., Winkler, R. J. Biol. Chem. (2005) [Pubmed]
  5. N-ras oncogene causes AP-2 transcriptional self-interference, which leads to transformation. Kannan, P., Buettner, R., Chiao, P.J., Yim, S.O., Sarkiss, M., Tainsky, M.A. Genes Dev. (1994) [Pubmed]
  6. A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Lee, D.Y., Hayes, J.J., Pruss, D., Wolffe, A.P. Cell (1993) [Pubmed]
  7. The sex-determining region of the human Y chromosome encodes a finger protein. Page, D.C., Mosher, R., Simpson, E.M., Fisher, E.M., Mardon, G., Pollack, J., McGillivray, B., de la Chapelle, A., Brown, L.G. Cell (1987) [Pubmed]
  8. Differences in patterns of complementation of the more common groups of xeroderma pigmentosum: possible implications. Giannelli, F., Pawsey, S.A., Avery, J.A. Cell (1982) [Pubmed]
  9. Assembly of transcriptionally active 5S RNA gene chromatin in vitro. Gottesfeld, J., Bloomer, L.S. Cell (1982) [Pubmed]
  10. Solution structure of the DNA-binding domain of the oestrogen receptor. Schwabe, J.W., Neuhaus, D., Rhodes, D. Nature (1990) [Pubmed]
  11. The high affinity alphaIIb beta3 integrin is involved in invasion of human melanoma cells. Trikha, M., Timar, J., Lundy, S.K., Szekeres, K., Cai, Y., Porter, A.T., Honn, K.V. Cancer Res. (1997) [Pubmed]
  12. Stem cell factor binding to retrovirus primer binding site silencers. Yamauchi, M., Freitag, B., Khan, C., Berwin, B., Barklis, E. J. Virol. (1995) [Pubmed]
  13. Anti-clumping factor A immunoglobulin reduces the duration of methicillin-resistant Staphylococcus aureus bacteremia in an experimental model of infective endocarditis. Vernachio, J., Bayer, A.S., Le, T., Chai, Y.L., Prater, B., Schneider, A., Ames, B., Syribeys, P., Robbins, J., Patti, J.M. Antimicrob. Agents Chemother. (2003) [Pubmed]
  14. Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression. Langerak, A.W., Williamson, K.A., Miyagawa, K., Hagemeijer, A., Versnel, M.A., Hastie, N.D. Genes Chromosomes Cancer (1995) [Pubmed]
  15. Interaction of HIV-1 Gag with the clathrin-associated adaptor AP-2. Batonick, M., Favre, M., Boge, M., Spearman, P., Höning, S., Thali, M. Virology (2005) [Pubmed]
  16. Molecular cloning, characterization, and chromosomal mapping of a novel human gene (GTF3A) that is highly homologous to Xenopus transcription factor IIIA. Arakawa, H., Nagase, H., Hayashi, N., Ogawa, M., Nagata, M., Fujiwara, T., Takahashi, E., Shin, S., Nakamura, Y. Cytogenet. Cell Genet. (1995) [Pubmed]
  17. Identification of a transcription factor IIIA-interacting protein. Moreland, R.J., Dresser, M.E., Rodgers, J.S., Roe, B.A., Conaway, J.W., Conaway, R.C., Hanas, J.S. Nucleic Acids Res. (2000) [Pubmed]
  18. Amphibian transcription factor IIIA proteins contain a sequence element functionally equivalent to the nuclear export signal of human immunodeficiency virus type 1 Rev. Fridell, R.A., Fischer, U., Lührmann, R., Meyer, B.E., Meinkoth, J.L., Malim, M.H., Cullen, B.R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  19. Purification and characterization of human transcription factor IIIA. Moorefield, B., Roeder, R.G. J. Biol. Chem. (1994) [Pubmed]
  20. The rabbit gene for 92-kDa matrix metalloproteinase. Role of AP1 and AP2 in cell type-specific transcription. Fini, M.E., Bartlett, J.D., Matsubara, M., Rinehart, W.B., Mody, M.K., Girard, M.T., Rainville, M. J. Biol. Chem. (1994) [Pubmed]
  21. Role and regulation of the thrombin receptor (PAR-1) in human melanoma. Tellez, C., Bar-Eli, M. Oncogene (2003) [Pubmed]
  22. Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways. Turner, B.C., Zhang, J., Gumbs, A.A., Maher, M.G., Kaplan, L., Carter, D., Glazer, P.M., Hurst, H.C., Haffty, B.G., Williams, T. Cancer Res. (1998) [Pubmed]
  23. cDNA clones reveal differences between human glial and endothelial cell platelet-derived growth factor A-chains. Tong, B.D., Auer, D.E., Jaye, M., Kaplow, J.M., Ricca, G., McConathy, E., Drohan, W., Deuel, T.F. Nature (1987) [Pubmed]
  24. Regulation of transcription factor AP-2 by the morphogen retinoic acid and by second messengers. Lüscher, B., Mitchell, P.J., Williams, T., Tjian, R. Genes Dev. (1989) [Pubmed]
  25. A variant of Glanzmann's thrombasthenia with abnormal glycoprotein IIb-IIIa complexes in the platelet membrane. Nurden, A.T., Rosa, J.P., Fournier, D., Legrand, C., Didry, D., Parquet, A., Pidard, D. J. Clin. Invest. (1987) [Pubmed]
  26. GLUT4 is internalized by a cholesterol-dependent nystatin-sensitive mechanism inhibited by insulin. Blot, V., McGraw, T.E. EMBO J. (2006) [Pubmed]
  27. A novel jasmonate- and elicitor-responsive element in the periwinkle secondary metabolite biosynthetic gene Str interacts with a jasmonate- and elicitor-inducible AP2-domain transcription factor, ORCA2. Menke, F.L., Champion, A., Kijne, J.W., Memelink, J. EMBO J. (1999) [Pubmed]
  28. Human transcription factor IIIC binds to its cognate promoter sequences in a metal coordinated fashion. Waldschmidt, R., Schneider, H.R., Seifart, K.H. Nucleic Acids Res. (1991) [Pubmed]
  29. DNA binding domain and subunit interactions of transcription factor IIIC revealed by dissection with poliovirus 3C protease. Shen, Y., Igo, M., Yalamanchili, P., Berk, A.J., Dasgupta, A. Mol. Cell. Biol. (1996) [Pubmed]
  30. P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA. Yoshida, Y., Izumi, H., Torigoe, T., Ishiguchi, H., Itoh, H., Kang, D., Kohno, K. Cancer Res. (2003) [Pubmed]
  31. Nitric oxide regulates shear stress-induced early growth response-1. Expression via the extracellular signal-regulated kinase pathway in endothelial cells. Chiu, J.J., Wung, B.S., Hsieh, H.J., Lo, L.W., Wang, D.L. Circ. Res. (1999) [Pubmed]
  32. NM23-H1 and NM23-H2 repress transcriptional activities of nuclease-hypersensitive elements in the platelet-derived growth factor-A promoter. Ma, D., Xing, Z., Liu, B., Pedigo, N.G., Zimmer, S.G., Bai, Z., Postel, E.H., Kaetzel, D.M. J. Biol. Chem. (2002) [Pubmed]
  33. In vitro methylation of nuclear respiratory factor-1 binding site suppresses the promoter activity of mitochondrial transcription factor A. Choi, Y.S., Kim, S., Kyu Lee, H., Lee, K.U., Pak, Y.K. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  34. Human platelet-derived growth factor A chain is transcriptionally repressed by the Wilms tumor suppressor WT1. Gashler, A.L., Bonthron, D.T., Madden, S.L., Rauscher, F.J., Collins, T., Sukhatme, V.P. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  35. FGF-1-induced platelet-derived growth factor-A chain gene expression in endothelial cells involves transcriptional activation by early growth response factor-1. Delbridge, G.J., Khachigian, L.M. Circ. Res. (1997) [Pubmed]
  36. Cloning and characterization of an evolutionarily divergent DNA-binding subunit of mammalian TFIIIC. Lagna, G., Kovelman, R., Sukegawa, J., Roeder, R.G. Mol. Cell. Biol. (1994) [Pubmed]
  37. Inhibition of host cell RNA polymerase III-mediated transcription by poliovirus: inactivation of specific transcription factors. Fradkin, L.G., Yoshinaga, S.K., Berk, A.J., Dasgupta, A. Mol. Cell. Biol. (1987) [Pubmed]
  38. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. El-Omar, E.M., Rabkin, C.S., Gammon, M.D., Vaughan, T.L., Risch, H.A., Schoenberg, J.B., Stanford, J.L., Mayne, S.T., Goedert, J., Blot, W.J., Fraumeni, J.F., Chow, W.H. Gastroenterology (2003) [Pubmed]
  39. Identification of platelet-derived growth factor A and B chains in human renal vascular rejection. Alpers, C.E., Davis, C.L., Barr, D., Marsh, C.L., Hudkins, K.L. Am. J. Pathol. (1996) [Pubmed]
  40. Regulation of platelet-derived growth factor-A chain by Krüppel-like factor 5: new pathway of cooperative activation with nuclear factor-kappaB. Aizawa, K., Suzuki, T., Kada, N., Ishihara, A., Kawai-Kowase, K., Matsumura, T., Sasaki, K., Munemasa, Y., Manabe, I., Kurabayashi, M., Collins, T., Nagai, R. J. Biol. Chem. (2004) [Pubmed]
  41. Purification of human transcription factor IIIA and its interaction with a chemically synthesized gene encoding human 5 S rRNA. Seifart, K.H., Wang, L., Waldschmidt, R., Jahn, D., Wingender, E. J. Biol. Chem. (1989) [Pubmed]
  42. cDNA cloning, DNA binding, and evolution of mammalian transcription factor IIIA. Hanas, J.S., Hocker, J.R., Cheng, Y.G., Lerner, M.R., Brackett, D.J., Lightfoot, S.A., Hanas, R.J., Madhusudhan, K.T., Moreland, R.J. Gene (2002) [Pubmed]
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