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 List of PDB id codes 1SP1​, 1SP2​, 1VA1​, 1VA2​, 1VA3​
Identifiers
Symbol	SP1
External IDs	OMIM: 189906 MGI: 98372 HomoloGene: 8276 ChEMBL: 6103 GeneCards: SP1 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II core promoter sequence-specific DNA binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription • RNA polymerase II repressing transcription factor binding • DNA binding • double-stranded DNA binding • sequence-specific DNA binding transcription factor activity • protein binding • protein C-terminus binding • transcription factor binding • zinc ion binding • histone acetyltransferase binding • enhancer binding • protein homodimerization activity • histone deacetylase binding • bHLH transcription factor binding • sequence-specific DNA binding • transcription regulatory region DNA binding • HMG box domain binding Cellular component • nucleus • nucleoplasm • nucleolus • cytoplasm • protein-DNA complex Biological process • ossification • trophectodermal cell differentiation • liver development • embryonic placenta development • transcription, DNA-dependent • regulation of transcription, DNA-dependent • transcription initiation from RNA polymerase II promoter • transforming growth factor beta receptor signaling pathway • gene expression • virus-host interaction • megakaryocyte differentiation • lung development • enucleate erythrocyte differentiation • positive regulation by host of viral transcription • cellular lipid metabolic process • small molecule metabolic process • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase II promoter • embryonic camera-type eye morphogenesis • embryonic skeletal system development • embryonic process involved in female pregnancy • definitive hemopoiesis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
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

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

Function

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.

Structure

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).

Applications

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]

Inhibitors

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

Interactions

Sp1 transcription factor has been shown to interact with:

• AATF,^[4]
• CEBPB,^[5][6]
• COL1A1,^[7]
• E2F1,^[8][9][10]
• FOSL1,^[11]
• GABPA,^[12]
• HDAC1,^{[4][13][14][15]}
• HDAC2,^[14][15][16]
• HMGA1,^[6]
• HCFC1,^[17][18]
• HTT,^[19]
• KLF6,^[20]
• MEF2C,^[21]
• MEF2D,^[22]
• MSX1,^[23]
• Myogenin,^[24]
• POU2F1,^[17][25]
• PPP1R13L,^[26]
• PSMC5,^[27][28]
• PML,^[29]
• RELA,^[30][31]
• SMAD3,^[32][33]
• SUMO1,^[27]
• SF1,^[34]
• TAL1,^[35] and
• UBC.^[27]

References

1. "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. doi:10.1128/MCB.23.6.1843-1855.2003. PMC 149455. PMID 12612060.
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. 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. 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. 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. 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. 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. 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. 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. 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.

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. doi:10.1074/jbc.M102604200. PMID 11340073.
• 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. doi:10.1111/j.1749-6632.1997.tb48521.x. PMID 9329821.
• Dyson N (1998). "The regulation of E2F by pRB-family proteins". Genes Dev. 12 (15): 2245–62. doi:10.1101/gad.12.15.2245. PMID 9694791.
• 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. doi:10.1016/S0960-0760(03)00230-9. PMID 12943729.
• 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. doi:10.1089/104454904773819789. PMID 15142377.
• 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. doi:10.2741/1403. PMID 15353294.
• Le Rouzic E, Benichou S (2005). "The Vpr protein from HIV-1: distinct roles along the viral life cycle". Retrovirology 2: 11. doi:10.1186/1742-4690-2-11. PMC 554975. PMID 15725353.
• 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. PMC 241184. PMID 1583736.
• 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. doi:10.1016/0888-7543(91)90114-T. PMID 1662663.
• 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. PMID 1912570.
• 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. doi:10.1073/pnas.88.19.8510. PMC 52538. PMID 1924310.
• 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. doi:10.1016/0092-8674(89)90606-5. PMID 2512012.
• 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. PMC 250732. PMID 2657100.
• Jackson SP, Tjian R (1988). "O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation". Cell 55 (1): 125–33. doi:10.1016/0092-8674(88)90015-3. PMID 3139301.
• 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. doi:10.1016/0092-8674(87)90594-0. PMID 3319186.
• 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. doi:10.1074/jbc.270.25.15320. PMID 7541039.
• 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. doi:10.1074/jbc.270.42.24989. PMID 7559627.
• 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. doi:10.1128/mcb.15.10.5444. PMC 230794. PMID 7565695.
• 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. doi:10.1074/jbc.270.43.25564. PMID 7592727.
• 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. doi:10.1016/1074-7613(95)90165-5. PMID 7621073.
• 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. doi:10.1016/0378-1119(95)00140-2. PMID 7622044.
• 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. doi:10.1161/CIRCRESAHA.107.167395. PMID 18258854.

External links

• Sp1 Transcription Factor at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook SP1

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