Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Shiro KoizumeEmail author
  • Yohei Miyagi
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101923


Historical Background

Specificity protein 1 (Sp1) is a member of the so-called Sp/Krüppel-like factor family that was first identified as a transcription factor binding to a GC-rich region of the SV40 early promoter region (Dynan and Tjian 1983). Unlike other members of this family, Sp1 is ubiquitously expressed, and this reflects its vital role in cell function. Sp1 structure and function are well characterized, with the transcription factor comprising 785 amino acid residues (Fig. 1) and contributing to the basal regulation of multiple targets including house-keeping genes. Sp1 generally regulates TATA-less gene promoters (Wierstra 2008; Vizcaíno et al. 2015). However, Sp1 can also augment activity of TATA-containing promoters via TATA-box binding protein (Vizcaíno et al. 2015). Sp1 typically binds double-stranded DNA containing GC-rich sequences via zinc finger motifs, thereafter recruiting the general transcription machinery to the target gene...
This is a preview of subscription content, log in to check access.


  1. Baylin S, Jones PA. A decade of exploring the cancer epigenome – biological and translational implications. Nat Rev Cancer. 2011;11:726–34.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Beishline K, Azizkhan-Clifford J. Sp1 and the ‘hallmarks of cancer’. FEBS J. 2015;282:224–58.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M, Nemes A, Temper V, Razin A, Cedar H. Sp1 elements protect a CpG island from de novo methylation. Nature. 1994;371:435–8.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Chang W-C, Hung J-J. Functional role of post-translational modifications of Sp1 in tumorigenesis. J Biomed Sci. 2012;19:94.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Clark SJ, Harrison J, Molloy PL. Sp1 binding is inhibited by (m)Cp(m)CpG methylation. Gene. 1997;195:67–71.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Courey AJ, Tjan R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell. 1988;55:887–98.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Darnell Jr JE. Transcription factors as targets for cancer therapy. Nat Rev Cancer. 2002;2:740–9.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Deaton AM, Bird AP. CpG island and the regulation of transcription. Genes Dev. 2011;25:1010–22.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Dynan WS, Tjian R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 1983;35:79–87.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Gaynor RB, Shieh BH, Klisak I, Sparkes RS, Lusis AJ. Localization of the transcription factor SP1 gene to human chromosome 12q12→q13.2. Cytogenet Cell Genet. 1993;64:210–2.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Hagenbuchner J, Ausserlechner MJ. Targeting transcription factors by small compounds–Current strategies and future implications. Biochem Pharmacol. 2016;107:1–13.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Harrington MA, Jones PA, Imagawa M, Karin M. Cytosine methylation does not affect binding of transcription factor Sp1. Proc Natl Acad Sci USA. 1988;85:2066–70.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Holler M, Westin G, Jiricny J, Schaffner W. Sp1 transcription factor binds DNA and activates transcription even when the binding site is CpG methylated. Genes Dev. 1988;2:1127–35.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Ito T, Kitamura H, Uwatoko C, Azumano M, Itoh K, Kuwahara J. Interaction of Sp1 zinc finger with transport factor in the nuclear localization of transcription factor Sp1. Biochem Biophys Res Commun. 2010;403:161–6.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Koizume S, Miyagi Y. Diverse mechanisms of Sp1-dependent transcriptional regulation potentially involved in the adaptive response of cancer cells to oxygen-deficient conditions. Cancers. 2016;8:2.CrossRefGoogle Scholar
  16. Macleod D, Charlton J, Mullins J, Bird A. Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev. 1994;8:2282–92.PubMedPubMedCentralCrossRefGoogle Scholar
  17. McConnell BB, Yang VW. Mammalian Kruppel-like factors in health and diseases. Physiol Rev. 2010;90:1337–81.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM, Snyder SH. Cystathionine g-lyase deficiency mediates neurodegeneration in Huntington’s disease. Nature. 2014;509:96–100.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Vizcaíno C, Mansilla S, Portugal J. Sp1 transcription factor: a long-standing target in cancer chemotherapy. Pharmacol Ther. 2015;152:111–24.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Wierstra I. Sp1: emerging roles-Beyond constitutive activation of TATA-less housekeeping genes. Biochem Biophys Res Commun. 2008;372:1–13.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Molecular Pathology and Genetics DivisionKanagawa Cancer Center Research InstituteYokohamaJapan