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Gene Review

Sp3  -  Sp3 transcription factor

Rattus norvegicus

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Disease relevance of Sp3

  • To test whether other members of the Sp family are direct targets of insulin action, we compared the levels of Sp1 and Sp3 proteins from nuclear extracts obtained from both insulin-treated and untreated rat hepatoma (H-411E) cells [1].

High impact information on Sp3

  • Increased expression of p27(Kip1) increases the level of Sp1 promoter binding to the GC box but does not change the level of Sp3 binding [2].
  • The results have demonstrated that Kir6.2 promoter possesses two regions regulating the promoter activity: a Foxa2-binding site (-1364 to -1210) and an Sp1/Sp3-binding site (-1035 to -939) [3].
  • Thus, regulation of Sp1/Sp3 recruitment to the promoter may represent a potential general mechanism for transcriptional control of target genes by signals passing through gap junctions [4].
  • Tyrosine phosphorylation of one Sp3 form was decreased, whereas phosphorylation of two other forms of Sp3 was increased in nuclear extracts of Ha-Ras-transformed cells [5].
  • Expression of several forms of Sp3 was increased in nuclear extracts of Ha-Ras-transformed fibroblasts compared with nontransformed cells [5].

Biological context of Sp3


Anatomical context of Sp3

  • Gap junctional communication modulates gene transcription by altering the recruitment of Sp1 and Sp3 to connexin-response elements in osteoblast promoters [4].
  • Because GC-box is a consensus site for binding of Sp transcription-factor family members, experiments were performed demonstrating that two Sp family members, Sp1 and Sp3, were present in testis cells from 9-day-old and adult rats and in pachytene primary spermatocytes and early spermatids [10].
  • This study was carried out to investigate the immunolocalization of Sp3 during the development of rat tooth germs [11].
  • Immunohistochemical localization of transcription factor Sp3 during dental enamel development in rat tooth germ [11].
  • Sp3 was found to be localized within the nuclei of cells in developing tooth germs; however, ameloblast nuclei showed variable intensities at different developmental stages [11].

Associations of Sp3 with chemical compounds


Physical interactions of Sp3

  • We identified an Sp1/Sp3 containing complex that assembles on a minimal element in the -70 to -57 region of the osteocalcin promoter in a gap junction-dependent manner [4].
  • Sp1 and Sp3 binding also occurred downstream from or overlapping the Egr-1 binding site in the rat alpha7 promoter [16].
  • Sp1 has been identified as one of the factors whose binding is lost, and in the present study we show that Sp3 binding is also abrogated by IGF-I, but in a selected manner [17].
  • Moreover, Sp1 and Sp3 proteins interacted with the proximal and the distal Sp1 sites in the nuclear extracts of gp600/megalin expressing cell lines [18].

Other interactions of Sp3


Analytical, diagnostic and therapeutic context of Sp3


  1. Insulin deprivation leads to deficiency of Sp1 transcription factor in H-411E hepatoma cells and in streptozotocin-induced diabetic ketoacidosis in the rat. Pan, X., Solomon, S.S., Borromeo, D.M., Martinez-Hernandez, A., Raghow, R. Endocrinology (2001) [Pubmed]
  2. The Sp1 family of transcription factors is involved in p27(Kip1)-mediated activation of myelin basic protein gene expression. Wei, Q., Miskimins, W.K., Miskimins, R. Mol. Cell. Biol. (2003) [Pubmed]
  3. Regulation of ATP-sensitive potassium channel subunit Kir6.2 expression in rat intestinal insulin-producing progenitor cells. Hashimoto, T., Nakamura, T., Maegawa, H., Nishio, Y., Egawa, K., Kashiwagi, A. J. Biol. Chem. (2005) [Pubmed]
  4. Gap junctional communication modulates gene transcription by altering the recruitment of Sp1 and Sp3 to connexin-response elements in osteoblast promoters. Stains, J.P., Lecanda, F., Screen, J., Towler, D.A., Civitelli, R. J. Biol. Chem. (2003) [Pubmed]
  5. Oncogenic Ha-Ras transformation modulates the transcription of the CTP:phosphocholine cytidylyltransferase alpha gene via p42/44MAPK and transcription factor Sp3. Bakovic, M., Waite, K., Vance, D.E. J. Biol. Chem. (2003) [Pubmed]
  6. Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene. Boylan, M.O., Jepeal, L.I., Wolfe, M.M. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  7. Identification of the proteins specifically binding to the rat LINE1 promoter. Fedorov, A.V., Lukyanov, D.V., Podgornaya, O.I. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  8. Sequence-selective DNA binding drugs mithramycin A and chromomycin A3 are potent inhibitors of neuronal apoptosis induced by oxidative stress and DNA damage in cortical neurons. Chatterjee, S., Zaman, K., Ryu, H., Conforto, A., Ratan, R.R. Ann. Neurol. (2001) [Pubmed]
  9. Sp1 and Sp3 regulate expression of the neuronal nicotinic acetylcholine receptor beta4 subunit gene. Bigger, C.B., Melnikova, I.N., Gardner, P.D. J. Biol. Chem. (1997) [Pubmed]
  10. H1t/GC-box and H1t/TE1 element are essential for promoter activity of the testis-specific histone H1t gene. Wilkerson, D.C., Wolfe, S.A., Grimes, S.R. Biol. Reprod. (2002) [Pubmed]
  11. Immunohistochemical localization of transcription factor Sp3 during dental enamel development in rat tooth germ. Lv, P., Jia, H.T., Gao, X.J. Eur. J. Oral Sci. (2006) [Pubmed]
  12. GLUT1 glucose transporter gene transcription is repressed by Sp3. Evidence for a regulatory role of Sp3 during myogenesis. Fandos, C., Sánchez-Feutrie, M., Santalucía, T., Viñals, F., Cadefau, J., Gumà, A., Cussó, R., Kaliman, P., Canicio, J., Palacín, M., Zorzano, A. J. Mol. Biol. (1999) [Pubmed]
  13. Carvedilol effectively blocks oxidative stress-mediated downregulation of sarcoplasmic reticulum Ca2+-ATPase 2 gene transcription through modification of Sp1 binding. Koitabashi, N., Arai, M., Tomaru, K., Takizawa, T., Watanabe, A., Niwano, K., Yokoyama, T., Wuytack, F., Periasamy, M., Nagai, R., Kurabayashi, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  14. Perinatal regulation of the ClC-2 chloride channel in lung is mediated by Sp1 and Sp3. Chu, S., Blaisdell, C.J., Liu, M.Z., Zeitlin, P.L. Am. J. Physiol. (1999) [Pubmed]
  15. Sp1 and Sp3 transcription factors mediate malondialdehyde-induced collagen alpha 1(I) gene expression in cultured hepatic stellate cells. García-Ruiz, I., de la Torre, P., Díaz, T., Esteban, E., Fernández, I., Muñoz-Yagüe, T., Solís-Herruzo, J.A. J. Biol. Chem. (2002) [Pubmed]
  16. Characterization of a rat neuronal nicotinic acetylcholine receptor alpha7 promoter. Nagavarapu, U., Danthi, S., Boyd, R.T. J. Biol. Chem. (2001) [Pubmed]
  17. Insulin-like growth factor-I regulates transcription of the elastin gene through a putative retinoblastoma control element. A role for Sp3 acting as a repressor of elastin gene transcription. Conn, K.J., Rich, C.B., Jensen, D.E., Fontanilla, M.R., Bashir, M.M., Rosenbloom, J., Foster, J.A. J. Biol. Chem. (1996) [Pubmed]
  18. Functional characterization of rat gp600/megalin promoter: combination of proximal Sp1 site and JCV repeat is important in rat gp600/megalin promoter activation. Zhao, J., Oleinikov, A.V., Oleinikova, I., Makker, S.P. Gene (2001) [Pubmed]
  19. Transcriptional regulation of the rat Mrp3 promoter in intestine cells. Tzeng, S.J., Huang, J.D. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  20. Ets-1 stimulates platelet-derived growth factor A-chain gene transcription and vascular smooth muscle cell growth via cooperative interactions with Sp1. Santiago, F.S., Khachigian, L.M. Circ. Res. (2004) [Pubmed]
  21. Functional analysis of the rat N-methyl-D-aspartate receptor 2A promoter: multiple transcription starts points, positive regulation by Sp factors, and translational regulation. Liu, A., Zhuang, Z., Hoffman, P.W., Bai, G. J. Biol. Chem. (2003) [Pubmed]
  22. Differential effects of heterogeneous nuclear ribonucleoprotein K on Sp1- and Sp3-mediated transcriptional activation of a neuronal nicotinic acetylcholine receptor promoter. Du, Q., Melnikova, I.N., Gardner, P.D. J. Biol. Chem. (1998) [Pubmed]
  23. Characterization of 5'-flanking region of rat somatostatin receptor sst2 gene: transcriptional regulatory elements and activation by Pitx1 and estrogen. Kimura, N., Tomizawa, S., Arai, K.N., Osamura, R.Y., Kimura, N. Endocrinology (2001) [Pubmed]
  24. Involvement of specific proteins (Sp1/Sp3) and nuclear factor Y in basal transcription of the distal promoter of the rat pyruvate carboxylase gene in beta-cells. Sunyakumthorn, P., Boonsaen, T., Boonsaeng, V., Wallace, J.C., Jitrapakdee, S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  25. Zinc finger transcription factors mediate high constitutive platelet-derived growth factor-B expression in smooth muscle cells derived from aortae of newborn rats. Rafty, L.A., Khachigian, L.M. J. Biol. Chem. (1998) [Pubmed]
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