sp2 transcription factor


Summary: A ubiquitously expressed Sp transcription factor that binds to the consensus DNA sequence GGGCGGGAC.

Top Publications

  1. Kingsley C, Winoto A. Cloning of GT box-binding proteins: a novel Sp1 multigene family regulating T-cell receptor gene expression. Mol Cell Biol. 1992;12:4251-61 pubmed
    ..As the GT box has also previously been shown to play a role in gene regulation of other genes, these newly isolated Sp2 and Sp3 proteins might regulate expression not only of the TCR gene but of other genes as well. ..
  2. Kim T, Chiera S, Linder K, Trempus C, Smart R, Horowitz J. Overexpression of transcription factor sp2 inhibits epidermal differentiation and increases susceptibility to wound- and carcinogen-induced tumorigenesis. Cancer Res. 2010;70:8507-16 pubmed publisher
    ..Our results directly support the likelihood that Sp2 overexpression occurring in various human cancers has significant functional effect. ..
  3. Baur F, Nau K, Sadic D, Allweiss L, Elsässer H, Gillemans N, et al. Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts. PLoS ONE. 2010;5:e9587 pubmed publisher
  4. Moorefield K, Yin H, Nichols T, Cathcart C, Simmons S, Horowitz J. Sp2 localizes to subnuclear foci associated with the nuclear matrix. Mol Biol Cell. 2006;17:1711-22 pubmed
    ..We conclude that Sp2 preferentially associates with the nuclear matrix and speculate that this subcellular localization plays an important role in the regulation of Sp2 function. ..
  5. Moorefield K, Fry S, Horowitz J. Sp2 DNA binding activity and trans-activation are negatively regulated in mammalian cells. J Biol Chem. 2004;279:13911-24 pubmed
    ..Taken together, our data indicate that Sp2 is functionally distinct relative to other Sp family members and suggest that Sp2 may play a unique role in cell physiology. ..
  6. Loziuk P, Meier F, Johnson C, Ghashghaei H, Muddiman D. TransOmic analysis of forebrain sections in Sp2 conditional knockout embryonic mice using IR-MALDESI imaging of lipids and LC-MS/MS label-free proteomics. Anal Bioanal Chem. 2016;408:3453-74 pubmed publisher
    ..In particular, step-specific altered abundances of nucleotides, lipids, and associated proteins were observed in the cerebral cortices of Sp2-cKO embryos. ..
  7. Burnett J, Miller Jensen K, Shah P, Arkin A, Schaffer D. Control of stochastic gene expression by host factors at the HIV promoter. PLoS Pathog. 2009;5:e1000260 pubmed publisher
    ..These results may have biomedical implications for the treatment of HIV latency. ..
  8. Azakie A, Fineman J, He Y. Sp3 inhibits Sp1-mediated activation of the cardiac troponin T promoter and is downregulated during pathological cardiac hypertrophy in vivo. Am J Physiol Heart Circ Physiol. 2006;291:H600-11 pubmed
    ..This observation is consistent with the in vitro activating function of Sp1 and inhibitory effects of Sp3 on activity of cTnT promoter constructs. Sp factor levels are modulated during the hypertrophic cardiac program in vivo. ..
  9. Wu J, Lim R. Regulation of inhibitor of differentiation gene 3 (Id3) expression by Sp2-motif binding factor in myogenic C2C12 cells: downregulation of DNA binding activity following skeletal muscle differentiation. Biochim Biophys Acta. 2005;1731:13-22 pubmed
    ..Our results reveal Id3 as a potential target for Sp2 and raise the possibility that acute activation and the chronic and maintained expression of Id3 gene might be regulated by different mechanisms. ..

More Information


  1. Bakovic M, Waite K, Vance D. Functional significance of Sp1, Sp2, and Sp3 transcription factors in regulation of the murine CTP:phosphocholine cytidylyltransferase alpha promoter. J Lipid Res. 2000;41:583-94 pubmed
    ..The results suggest that the level of expression of the CTalpha gene will depend on the cell type, the availability of Sp proteins, and the structure and organization of three cis-acting elements. ..
  2. Phan D, Cheng C, Galfione M, Vakar Lopez F, Tunstead J, Thompson N, et al. Identification of Sp2 as a transcriptional repressor of carcinoembryonic antigen-related cell adhesion molecule 1 in tumorigenesis. Cancer Res. 2004;64:3072-8 pubmed
    ..Our studies show that transcriptional repression by Sp2 represents one mechanism by which CEACAM1 tumor suppressor gene is down-regulated in prostate cancer. ..
  3. Terrados G, Finkernagel F, Stielow B, Sadic D, Neubert J, Herdt O, et al. Genome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes. Nucleic Acids Res. 2012;40:7844-57 pubmed publisher
    ..Our results establish Sp2 as a sequence-specific regulator of vitally important genes. ..
  4. Carbone G, McGuffie E, Collier A, Catapano C. Selective inhibition of transcription of the Ets2 gene in prostate cancer cells by a triplex-forming oligonucleotide. Nucleic Acids Res. 2003;31:833-43 pubmed
    ..This anti-transcriptional approach may be useful to examine the effects of selective downregulation of Ets2 expression and may have therapeutic applications. ..
  5. Scherrer S, Rice D, Heckert L. Expression of steroidogenic factor 1 in the testis requires an interactive array of elements within its proximal promoter. Biol Reprod. 2002;67:1509-21 pubmed
  6. Dachet C, Poirier O, Cambien F, Chapman J, Rouis M. New functional promoter polymorphism, CETP/-629, in cholesteryl ester transfer protein (CETP) gene related to CETP mass and high density lipoprotein cholesterol levels: role of Sp1/Sp3 in transcriptional regulation. Arterioscler Thromb Vasc Biol. 2000;20:507-15 pubmed
    ..These results indicate that Sp1 and/or Sp3 repress CETP promoter activity, whereas nuclear factors binding the C allele are without effect on promoter expression. ..
  7. Frehlick L, Prado A, Calestagne Morelli A, Ausio J. Characterization of the PL-I-related SP2 protein from Xenopus. Biochemistry. 2007;46:12700-8 pubmed
    ..However, its interaction with circular DNA does not exhibit an enhanced preference for the supercoiled conformation, and it appears to be mainly driven by ionic interactions. ..
  8. LeVan T, Bloom J, Bailey T, Karp C, Halonen M, Martinez F, et al. A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity. J Immunol. 2001;167:5838-44 pubmed
    ..Variation in a key gene of innate immunity may be important for the pathogenesis of allergy and inflammatory disease through gene-by-gene and/or gene-by-environment interactions. ..
  9. Ansari K, Hussain I, Das H, Mandal S. Overexpression of human histone methylase MLL1 upon exposure to a food contaminant mycotoxin, deoxynivalenol. FEBS J. 2009;276:3299-307 pubmed publisher
    ..These results demonstrated that MLL1 gene expression is sensitive to toxic stress and Sp1 plays crucial roles in the stress-induced upregulation of MLL1. ..
  10. Xie J, Yin H, Nichols T, Yoder J, Horowitz J. Sp2 is a maternally inherited transcription factor required for embryonic development. J Biol Chem. 2010;285:4153-64 pubmed publisher
  11. Magan N, Szremska A, Isaacs R, Stowell K. Modulation of DNA topoisomerase II alpha promoter activity by members of the Sp (specificity protein) and NF-Y (nuclear factor Y) families of transcription factors. Biochem J. 2003;374:723-9 pubmed
    ..Sp1 and NF-Y were both found to be transcriptional modulators with activator or repressor functions depending on protein/DNA context. Moreover, a functional interaction between Sp1 and NF-Y bound at proximal elements was observed. ..
  12. Chen W, Zhou H, Ye L, Zhan B. Overexpression of SULT2B1b Promotes Angiogenesis in Human Gastric Cancer. Cell Physiol Biochem. 2016;38:1040-54 pubmed publisher
  13. Liang H, Xiao G, Yin H, Hippenmeyer S, Horowitz J, Ghashghaei H. Neural development is dependent on the function of specificity protein 2 in cell cycle progression. Development. 2013;140:552-61 pubmed publisher
    ..Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain. ..
  14. Li X, Mertens Talcott S, Zhang S, Kim K, Ball J, Safe S. MicroRNA-27a Indirectly Regulates Estrogen Receptor {alpha} Expression and Hormone Responsiveness in MCF-7 Breast Cancer Cells. Endocrinology. 2010;151:2462-73 pubmed publisher
    ..Thus, miR-27a indirectly regulates E2-responsiveness in MCF-7 cells through suppression of ZBTB10, thereby enhancing expression of ERalpha. ..
  15. Yin H, Nichols T, Horowitz J. Transcription of mouse Sp2 yields alternatively spliced and sub-genomic mRNAs in a tissue- and cell-type-specific fashion. Biochim Biophys Acta. 2010;1799:520-31 pubmed publisher
  16. Lee J, Kosaras B, Aleyasin H, Han J, Park D, Ratan R, et al. Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response. FASEB J. 2006;20:2375-7 pubmed
    ..These results indicate that in primary neurons Sp1 and Sp3 play an essential role in the modulation of COX-2 transcription, which mediates neuronal homeostasis and survival by preventing DNA damage in response to neuronal stress. ..
  17. Kaufman C, Sinha S, Bolotin D, Fan J, Fuchs E. Dissection of a complex enhancer element: maintenance of keratinocyte specificity but loss of differentiation specificity. Mol Cell Biol. 2002;22:4293-308 pubmed
    ..Through mixing and matching of these modules, additional levels of specificity are obtained, indicating that both transcriptional repressors and activators govern the specificity. ..
  18. Sheng Y, Li J, Dufau M, Tsai Morris C. The gonadotropin-regulated long-chain acyl CoA synthetase gene: a novel downstream Sp1/Sp3 binding element critical for transcriptional promoter activity. Gene. 2005;360:20-6 pubmed
    ..Thus, functional analyses of this promoter domain indicate that transcription of GR-LACS gene requires an Sp1/Sp3 binding element downstream of the transcriptional start sites which is essential for basal promoter activity. ..
  19. Lee Y, Higashi Y, Luu C, Shimizu C, Strott C. Sp1 elements in SULT2B1b promoter and 5'-untranslated region of mRNA: Sp1/Sp2 induction and augmentation by histone deacetylase inhibition. FEBS Lett. 2005;579:3639-45 pubmed
    ..Sp1 and Sp2 transcription factors identified by supershift analyses induced reporter gene activity, an effect markedly augmented by histone deacetylase inhibition. ..
  20. Hammer F, Compagnone N, Vigne J, Bair S, Mellon S. Transcriptional regulation of P450scc gene expression in the embryonic rodent nervous system. Endocrinology. 2004;145:901-12 pubmed
    ..Thus, members of the Sp transcription family play a role in activating P450scc gene transcription in the nervous system, and Ku may further augment this activation. ..
  21. Letourneur M, Valentino L, Travagli Gross J, Bertoglio J, Pierre J. Sp2 regulates interferon-gamma-mediated socs1 gene expression. Mol Immunol. 2009;46:2151-60 pubmed publisher
    ..Despite the absence of Sp2 in the 5'-upstream sequence of the human promoter, silencing of Sp2 by RNA interference clearly demonstrated that Sp2 is required for IFN-gamma-induced regulation of socs1 mRNA both in human and mouse. ..
  22. Scohy S, Van Vooren P, Szpirer C, Szpirer J. Assignment1 of Sp genes to rat chromosome bands 7q36 (Sp1), 10q31-->q32.1 (Sp2), 3q24-->q31 (Sp3) and 6q33 (Sp4) and of the SP2 gene to human chromosome bands 17q21.3-->q22 by in situ hybridization. Cytogenet Cell Genet. 1998;81:273-4 pubmed