Sp1 transcription factor

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Sp1 transcription factor
Protein SP1 PDB 1sp1.png
NMR structure of the SP1 DNA-binding motif.
PDB rendering based on 1sp1.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbol SP1
External IDs OMIM189906 MGI98372 HomoloGene8276 ChEMBL: 6103 GeneCards: SP1 Gene
RNA expression pattern
PBB GE SP1 214732 at tn.png
More reference expression data
Species Human Mouse
Entrez 6667 20683
Ensembl ENSG00000185591 ENSMUSG00000001280
UniProt P08047 O89090
RefSeq (mRNA) NM_001251825 NM_013672
RefSeq (protein) NP_001238754 NP_038700
Location (UCSC) Chr 12:
53.77 – 53.81 Mb
Chr 15:
102.41 – 102.44 Mb
PubMed search [1] [2]

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. ^ a b "Entrez Gene: Sp1 transcription factor". 
  2. ^ Wormke M, Stoner M, Saville B, Walker K, Abdelrahim M, Burghardt R et al. (March 2003). "The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes". Mol. Cell. Biol. 23 (6): 1843–55. doi:10.1128/MCB.23.6.1843-1855.2003. PMC 149455. PMID 12612060. 
  3. ^ Prasanna K, Shilpa P, Salimath B (2009). "Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription". 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 et al. (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 Y, Tseng H, Chen L, Chen B, Chang W (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. ^ 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. doi:10.1128/MCB.23.8.2720-2732.2003. PMC 152545. PMID 12665574. 
  7. ^ Li L, Artlett C, Jimenez S, Hall D, 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 S, Black A, Kostic D, Pajovic S, Hoover C, Azizkhan J (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. PMC 231152. PMID 8657141. 
  11. ^ Evellin S, Galvagni F, Zippo A, Neri F, Orlandini M, Incarnato D et al. (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. 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 P (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. ^ a b Zhang Y, Dufau M (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. ^ a b Sun J, Chen H, Moniwa M, Litchfield D, Seto E, Davie J (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 T (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. ^ 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. doi:10.1023/A:1007177623283. PMID 10976766. 
  18. ^ Wysocka J, Myers M, Laherty C, Eisenman R, 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 S, Cheng A, Zhou H, Lam S, Rao M, Li H et al. (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 L, Sánchez-Elsner T, Sanz-Rodriguez F, Kojima S, Shimada J, Guerrero-Esteo M et al. (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 J, Brent R et al. (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 S, Shin H, Han T (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 ( Pt 3) (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 A, 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 J, Asamitsu K, Sarol L et al. (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. ^ a b c Wang Y, Chuang J, Shen M, Yang W, Chang W, Hung J (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 M, Paterson A, Kudlow J (2000). "Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1". Biochem. J. 348 Pt 2 (2): 281–9. doi:10.1042/0264-6021:3480281. PMC 1221064. PMID 10816420. 
  29. ^ Vallian S, Chin K, Chang K (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 P, Berk J, Rishikof D, Foster J, Humphries D, Ricupero D et al. (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 T (1994). "Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1". J. Virol. 68 (11): 7131–8. PMC 237152. PMID 7933095. 
  32. ^ Botella L, 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 A, Schnaper H (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 C, Porcher C et al. (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.