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Sp1 transcription factor

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Title: Sp1 transcription factor  
Author: World Heritage Encyclopedia
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Subject: Transcription factor, Apoptosis-antagonizing transcription factor, KLF6, GABPA, MEF2D
Collection: Transcription Factors
Publisher: World Heritage Encyclopedia

Sp1 transcription factor

Sp1 transcription factor
NMR structure of the SP1 DNA-binding motif.
PDB rendering based on 1sp1.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs ChEMBL: GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.[1]


  • Function 1
  • Structure 2
  • Applications 3
  • Inhibitors 4
  • Interactions 5
  • References 6
  • Further reading 7
  • External links 8


The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. Post-translational modifications such as phosphorylation, acetylation, glycosylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor.[1]

In the SV40 virus, Sp1 binds to the GC boxes in the regulatory region (RR) of the genome.


SP1 belongs to the Sp/KLF family of transcription factors. The protein is 785 amino acids long, with a molecular weight of 81 kDA. The SP1 transcription factor contains a zinc finger protein motif, by which it binds directly to DNA and enhances gene transcription. Its zinc fingers are of the Cys2/His2 type and bind the consensus sequence 5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3' (GC box element).


Sp1 has been used as a control protein to compare with when studying the increase or decrease of the aryl hydrocarbon receptor and/or the estrogen receptor, since it binds to both and generally remains at a relatively constant level.[2]


Withaferin A, a sterodial lactone from Withania Somnifera plant is known to inhibit Sp1 transcription factor.[3]


Sp1 transcription factor has been shown to interact with:


  1. ^ a b "Entrez Gene: Sp1 transcription factor". 
  2. ^ Wormke M, Stoner M, Saville B, Walker K, Abdelrahim M, Burghardt R, Safe S (March 2003). "The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes". Mol. Cell. Biol. 23 (6): 1843–55.  
  3. ^ Prasanna KS, Shilpa P, Salimath BP (2009). "Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription" (PDF). Current Trends in Biotechnology and Pharmacy 3 (2): 138–148. 
  4. ^ a b Di Padova M, Bruno T, De Nicola F, Iezzi S, D'Angelo C, Gallo R, Nicosia D, Corbi N, Biroccio A, Floridi A, Passananti C, Fanciulli M (2003). "Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter". J. Biol. Chem. 278 (38): 36496–504.  
  5. ^ Liu YW, Tseng HP, Chen LC, Chen BK, Chang WC (2003). "Functional cooperation of simian virus 40 promoter factor 1 and CCAAT/enhancer-binding protein beta and delta in lipopolysaccharide-induced gene activation of IL-10 in mouse macrophages". J. Immunol. 171 (2): 821–8.  
  6. ^ a b Foti D, Iuliano R, Chiefari E, Brunetti A (2003). "A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription". Mol. Cell. Biol. 23 (8): 2720–32.  
  7. ^ Li L, Artlett CM, Jimenez SA, Hall DJ, Varga J (1995). "Positive regulation of human alpha 1 (I) collagen promoter activity by transcription factor Sp1". Gene 164 (2): 229–34.  
  8. ^ Lin SY, Black AR, Kostic D, Pajovic S, Hoover CN, Azizkhan JC (1996). "Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction". Mol. Cell. Biol. 16 (4): 1668–75.  
  9. ^ Rotheneder H, Geymayer S, Haidweger E (1999). "Transcription factors of the Sp1 family: interaction with E2F and regulation of the murine thymidine kinase promoter". J. Mol. Biol. 293 (5): 1005–15.  
  10. ^ Karlseder J, Rotheneder H, Wintersberger E (1996). "Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F". Mol. Cell. Biol. 16 (4): 1659–67.  
  11. ^ Evellin S, Galvagni F, Zippo A, Neri F, Orlandini M, Incarnato D, Dettori D, Neubauer S, Kessler H, Wagner EF, Oliviero S (2013). "FOSL1 controls the assembly of endothelial cells into capillary tubes by direct repression of αv and β3 integrin transcription". Mol. Cell. Biol. 33 (6): 1198–209.  
  12. ^ Galvagni F, Capo S, Oliviero S (2001). "Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter". J. Mol. Biol. 306 (5): 985–96.  
  13. ^ Singh J, Murata K, Itahana Y, Desprez PY (2002). "Constitutive expression of the Id-1 promoter in human metastatic breast cancer cells is linked with the loss of NF-1/Rb/HDAC-1 transcription repressor complex". Oncogene 21 (12): 1812–22.  
  14. ^ a b Zhang Y, Dufau ML (2002). "Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex". J. Biol. Chem. 277 (36): 33431–8.  
  15. ^ a b Sun JM, Chen HY, Moniwa M, Litchfield DW, Seto E, Davie JR (2002). "The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2". J. Biol. Chem. 277 (39): 35783–6.  
  16. ^ Won J, Yim J, Kim TK (2002). "Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells". J. Biol. Chem. 277 (41): 38230–8.  
  17. ^ a b Gunther M, Laithier M, Brison O (2000). "A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening". Mol. Cell. Biochem. 210 (1-2): 131–42.  
  18. ^ Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W (2003). "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1". Genes Dev. 17 (7): 896–911.  
  19. ^ Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, Li XJ (2002). "Interaction of Huntington disease protein with transcriptional activator Sp1". Mol. Cell. Biol. 22 (5): 1277–87.  
  20. ^ Botella LM, Sánchez-Elsner T, Sanz-Rodriguez F, Kojima S, Shimada J, Guerrero-Esteo M, Cooreman MP, Ratziu V, Langa C, Vary CP, Ramirez JR, Friedman S, Bernabéu C (2002). "Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury". Blood 100 (12): 4001–10.  
  21. ^ Krainc D, Bai G, Okamoto S, Carles M, Kusiak JW, Brent RN, Lipton SA (1998). "Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1". J. Biol. Chem. 273 (40): 26218–24.  
  22. ^ Park SY, Shin HM, Han TH (2002). "Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter". Mol. Immunol. 39 (1-2): 25–30.  
  23. ^ Shetty S, Takahashi T, Matsui H, Ayengar R, Raghow R (1999). "Transcriptional autorepression of Msx1 gene is mediated by interactions of Msx1 protein with a multi-protein transcriptional complex containing TATA-binding protein, Sp1 and cAMP-response-element-binding protein-binding protein (CBP/p300)". Biochem. J. 339 ( Pt 3) (3): 751–8.  
  24. ^ Biesiada E, Hamamori Y, Kedes L, Sartorelli V (1999). "Myogenic basic helix-loop-helix proteins and Sp1 interact as components of a multiprotein transcriptional complex required for activity of the human cardiac alpha-actin promoter". Mol. Cell. Biol. 19 (4): 2577–84.  
  25. ^ Ström AC, Forsberg M, Lillhager P, Westin G (1996). "The transcription factors Sp1 and Oct-1 interact physically to regulate human U2 snRNA gene expression". Nucleic Acids Res. 24 (11): 1981–6.  
  26. ^ Takada N, Sanda T, Okamoto H, Yang JP, Asamitsu K, Sarol L, Kimura G, Uranishi H, Tetsuka T, Okamoto T (2002). "RelA-associated inhibitor blocks transcription of human immunodeficiency virus type 1 by inhibiting NF-kappaB and Sp1 actions". J. Virol. 76 (16): 8019–30.  
  27. ^ a b c Wang YT, Chuang JY, Shen MR, Yang WB, Chang WC, Hung JJ (2008). "Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process". J. Mol. Biol. 380 (5): 869–85.  
  28. ^ Su K, Yang X, Roos MD, Paterson AJ, Kudlow JE (2000). "Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1". Biochem. J. 348 Pt 2 (2): 281–9.  
  29. ^ Vallian S, Chin KV, Chang KS (1998). "The promyelocytic leukemia protein interacts with Sp1 and inhibits its transactivation of the epidermal growth factor receptor promoter". Mol. Cell. Biol. 18 (12): 7147–56.  
  30. ^ Kuang PP, Berk JL, Rishikof DC, Foster JA, Humphries DE, Ricupero DA, Goldstein RH (2002). "NF-kappaB induced by IL-1beta inhibits elastin transcription and myofibroblast phenotype". Am. J. Physiol., Cell Physiol. 283 (1): C58–65.  
  31. ^ Sif S, Gilmore TD (1994). "Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1". J. Virol. 68 (11): 7131–8.  
  32. ^ Botella LM, Sánchez-Elsner T, Rius C, Corbí A, Bernabéu C (2001). "Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation". J. Biol. Chem. 276 (37): 34486–94.  
  33. ^ Poncelet AC, Schnaper HW (2001). "Sp1 and Smad proteins cooperate to mediate transforming growth factor-beta 1-induced alpha 2(I) collagen expression in human glomerular mesangial cells". J. Biol. Chem. 276 (10): 6983–92.  
  34. ^ Sugawara T, Saito M, Fujimoto S (2000). "Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression". Endocrinology 141 (8): 2895–903.  
  35. ^ Lécuyer E, Herblot S, Saint-Denis M, Martin R, Begley CG, Porcher C, Orkin SH, Hoang T (2002). "The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1". Blood 100 (7): 2430–40.  

Further reading

  • Dreier B, Beerli RR, Segal DJ, Flippin JD, Barbas CF (2001). "Development of zinc finger domains for recognition of the 5'-ANN-3' family of DNA sequences and their use in the construction of artificial transcription factors". J. Biol. Chem. 276 (31): 29466–78.  
  • Tseng L, Gao J, Mazella J, Zhu HH, Lane B (1997). "Differentiation-dependent and cell-specific regulation of the hIGFBP-1 gene in human endometrium". Ann. N. Y. Acad. Sci. 828: 27–37.  
  • Dyson N (1998). "The regulation of E2F by pRB-family proteins". Genes Dev. 12 (15): 2245–62.  
  • Zhang Y, Dufau ML (2003). "Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes". J. Steroid Biochem. Mol. Biol. 85 (2-5): 401–14.  
  • Kino T, Pavlakis GN (2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA Cell Biol. 23 (4): 193–205.  
  • Seelamgari A, Maddukuri A, Berro R, de la Fuente C, Kehn K, Deng L, Dadgar S, Bottazzi ME, Ghedin E, Pumfery A, Kashanchi F (2004). "Role of viral regulatory and accessory proteins in HIV-1 replication". Front. Biosci. 9: 2388–413.  
  • Le Rouzic E, Benichou S (2005). "The Vpr protein from HIV-1: distinct roles along the viral life cycle". Retrovirology 2: 11.  
  • Kamine J, Chinnadurai G (1992). "Synergistic activation of the human immunodeficiency virus type 1 promoter by the viral Tat protein and cellular transcription factor Sp1". J. Virol. 66 (6): 3932–6.  
  • Szpirer J, Szpirer C, Riviere M, Levan G, Marynen P, Cassiman JJ, Wiese R, DeLuca HF (1991). "The Sp1 transcription factor gene (SP1) and the 1,25-dihydroxyvitamin D3 receptor gene (VDR) are colocalized on human chromosome arm 12q and rat chromosome 7". Genomics 11 (1): 168–73.  
  • Gumucio DL, Rood KL, Blanchard-McQuate KL, Gray TA, Saulino A, Collins FS (1991). "Interaction of Sp1 with the human gamma globin promoter: binding and transactivation of normal and mutant promoters". Blood 78 (7): 1853–63.  
  • Kamine J, Subramanian T, Chinnadurai G (1991). "Sp1-dependent activation of a synthetic promoter by human immunodeficiency virus type 1 Tat protein". Proc. Natl. Acad. Sci. U.S.A. 88 (19): 8510–4.  
  • Courey AJ, Holtzman DA, Jackson SP, Tjian R (1989). "Synergistic activation by the glutamine-rich domains of human transcription factor Sp1". Cell 59 (5): 827–36.  
  • Harrich D, Garcia J, Wu F, Mitsuyasu R, Gonazalez J, Gaynor R (1989). "Role of SP1-binding domains in in vivo transcriptional regulation of the human immunodeficiency virus type 1 long terminal repeat". J. Virol. 63 (6): 2585–91.  
  • Jackson SP, Tjian R (1988). "O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation". Cell 55 (1): 125–33.  
  • Kadonaga JT, Carner KR, Masiarz FR, Tjian R (1987). "Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain". Cell 51 (6): 1079–90.  
  • Zhang R, Min W, Sessa WC (1995). "Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells". J. Biol. Chem. 270 (25): 15320–6.  
  • Hagen G, Dennig J, Preiss A, Beato M, Suske G (1995). "Functional analyses of the transcription factor Sp4 reveal properties distinct from Sp1 and Sp3". J. Biol. Chem. 270 (42): 24989–94.  
  • Datta PK, Raychaudhuri P, Bagchi S (1995). "Association of p107 with Sp1: genetically separable regions of p107 are involved in regulation of E2F- and Sp1-dependent transcription". Mol. Cell. Biol. 15 (10): 5444–52.  
  • Wang L, Mukherjee S, Jia F, Narayan O, Zhao LJ (1995). "Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Sp1 and trans-activation of viral long terminal repeat". J. Biol. Chem. 270 (43): 25564–9.  
  • Howcroft TK, Palmer LA, Brown J, Rellahan B, Kashanchi F, Brady JN, Singer DS (1995). "HIV Tat represses transcription through Sp1-like elements in the basal promoter". Immunity 3 (1): 127–38.  
  • Ferrari N, Desmarais D, Royal A (1995). "Transcriptional activation of the neuronal peripherin-encoding gene depends on a G + C-rich element that binds Sp1 in vitro and in vivo". Gene 159 (2): 159–65.  
  • Tan NY, Midgley VC, Kavurma MM, Santiago FS, Luo X, Peden R, Fahmy RG, Berndt MC, Molloy MP, Khachigian LM (2008). "Angiotensin II-inducible platelet-derived growth factor-D transcription requires specific Ser/Thr residues in the second zinc finger region of Sp1". Circ. Res. 102 (4): e38–51.  

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