Sp1 transcription factor

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


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. 1.0 1.1 "Entrez Gene: Sp1 transcription factor".
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  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. 4.0 4.1 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. doi:10.1074/jbc.M306694200. PMID 12847090.
  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. doi:10.4049/jimmunol.171.2.821. PMID 12847250.
  6. 6.0 6.1 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. doi:10.1128/MCB.23.8.2720-2732.2003. PMC 152545. PMID 12665574.
  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. doi:10.1016/0378-1119(95)00508-4. PMID 7590335.
  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. PMC 231153. PMID 8657142.
  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. doi:10.1006/jmbi.1999.3213. PMID 10547281.
  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. doi:10.1128/mcb.16.4.1659. PMC 231152. PMID 8657141.
  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. doi:10.1128/MCB.01054-12. PMC 3592019. PMID 23319049.
  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. doi:10.1006/jmbi.2000.4335. PMID 11237613.
  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. doi:10.1038/sj.onc.1205252. PMID 11896613.
  14. 14.0 14.1 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. doi:10.1074/jbc.M204417200. PMID 12091390.
  15. 15.0 15.1 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. doi:10.1074/jbc.C200378200. PMID 12176973.
  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. doi:10.1074/jbc.M206064200. PMID 12151407.
  17. 17.0 17.1 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. doi:10.1023/A:1007177623283. PMID 10976766.
  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. doi:10.1101/gad.252103. PMC 196026. PMID 12670868.
  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. doi:10.1128/MCB.22.5.1277-1287.2002. PMC 134707. PMID 11839795.
  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. doi:10.1182/blood.V100.12.4001. PMID 12433697.
  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. doi:10.1074/jbc.273.40.26218. PMID 9748305.
  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. doi:10.1016/S0161-5890(02)00055-X. PMID 12213324.
  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 (3): 751–8. doi:10.1042/0264-6021:3390751. PMC 1220213. PMID 10215616.
  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. PMC 84050. PMID 10082523.
  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. doi:10.1093/nar/24.11.1981. PMC 145891. PMID 8668525.
  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. doi:10.1128/JVI.76.16.8019-8030.2002. PMC 155123. PMID 12134007.
  27. 27.0 27.1 27.2 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. doi:10.1016/j.jmb.2008.05.043. PMID 18572193.
  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 (2): 281–9. doi:10.1042/0264-6021:3480281. PMC 1221064. PMID 10816420.
  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. PMC 109296. PMID 9819401.
  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. doi:10.1152/ajpcell.00314.2001. PMID 12055073.
  31. Sif S, Gilmore TD (1994). "Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1". J. Virol. 68 (11): 7131–8. PMC 237152. PMID 7933095.
  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. doi:10.1074/jbc.M011611200. PMID 11432852.
  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. doi:10.1074/jbc.M006442200. PMID 11114293.
  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. doi:10.1210/en.141.8.2895. PMID 10919277.
  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. doi:10.1182/blood-2002-02-0568. PMID 12239153.

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.