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Sp1 transcription factor

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Sp1 transcription factor

PDB rendering based on 1sp1.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
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
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 [1] [2]

Sp1, also known as Specificity Protein 1, is a human transcription factor involved in gene expression in the early development of an organism. It belongs to the Sp/KLF family of transcription factors. The protein is 785 amino acids long, with a molecular weight of 81 kDA.[1] 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). It was discovered in 1983 and has since been modified to form Sp1C, which has a zinc finger protein DNA-binding domain.

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

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[33].

Contents

[edit] Interactions

Sp1 transcription factor has been shown to interact with MEF2C,[3] MEF2D,[4] E2F1,[5][6][7] POU2F1,[8][9] Host cell factor C1,[9][10] RELA,[11][12] CEBPB,[13][14] HMGA1,[14] MSX1,[15] GABPA,[16] Small ubiquitin-related modifier 1,[17] Mothers against decapentaplegic homolog 3,[18][19] HDAC1,[20][21][22][23] Histone deacetylase 2,[22][23][24] Huntingtin,[25] KLF6,[26] PSMC5,[17][27] Apoptosis-antagonizing transcription factor,[20] PPP1R13L,[28] Steroidogenic factor 1,[29] Myogenin,[30] TAL1,[31] Promyelocytic leukemia protein[32] and Ubiquitin C.[17]

[edit] References

  1. ^ See UniProtKB entry
  2. ^ Wormke M, Stoner M, Saville B, 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. ^ Krainc, D; Bai G, Okamoto S, Carles M, Kusiak J W, Brent R N, Lipton S A (October 1998). "Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1". J. Biol. Chem. (UNITED STATES) 273 (40): 26218–24. doi:10.1074/jbc.273.40.26218. ISSN 0021-9258. PMID 9748305. 
  4. ^ Park, So-Youn; Shin Hyun-Mu, Han Tae-Hee (September 2002). "Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter". Mol. Immunol. (England) 39 (1-2): 25–30. doi:10.1016/S0161-5890(02)00055-X. ISSN 0161-5890. PMID 12213324. 
  5. ^ Lin, S Y; Black A R, Kostic D, Pajovic S, Hoover C N, Azizkhan J C (April 1996). "Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction". Mol. Cell. Biol. (UNITED STATES) 16 (4): 1668–75. ISSN 0270-7306. PMC 231153. PMID 8657142. 
  6. ^ Rotheneder, H; Geymayer S, Haidweger E (November 1999). "Transcription factors of the Sp1 family: interaction with E2F and regulation of the murine thymidine kinase promoter". J. Mol. Biol. (ENGLAND) 293 (5): 1005–15. doi:10.1006/jmbi.1999.3213. ISSN 0022-2836. PMID 10547281. 
  7. ^ Karlseder, J; Rotheneder H, Wintersberger E (April 1996). "Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F". Mol. Cell. Biol. (UNITED STATES) 16 (4): 1659–67. ISSN 0270-7306. PMC 231152. PMID 8657141. 
  8. ^ Ström, A C; Forsberg M, Lillhager P, Westin G (June 1996). "The transcription factors Sp1 and Oct-1 interact physically to regulate human U2 snRNA gene expression". Nucleic Acids Res. (ENGLAND) 24 (11): 1981–6. doi:10.1093/nar/24.11.1981. ISSN 0305-1048. PMC 145891. PMID 8668525. 
  9. ^ a b Gunther, M; Laithier M, Brison O (July 2000). "A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening". Mol. Cell. Biochem. (NETHERLANDS) 210 (1-2): 131–42. doi:10.1023/A:1007177623283. ISSN 0300-8177. PMID 10976766. 
  10. ^ Wysocka, Joanna; Myers Michael P, Laherty Carol D, Eisenman Robert N, Herr Winship (April 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. (United States) 17 (7): 896–911. doi:10.1101/gad.252103. ISSN 0890-9369. PMC 196026. PMID 12670868. 
  11. ^ Kuang, Ping-Ping; Berk John L, Rishikof David C, Foster Judith A, Humphries Donald E, Ricupero Dennis A, Goldstein Ronald H (July 2002). "NF-kappaB induced by IL-1beta inhibits elastin transcription and myofibroblast phenotype". Am. J. Physiol., Cell Physiol. (United States) 283 (1): C58–65. doi:10.1152/ajpcell.00314.2001. ISSN 0363-6143. PMID 12055073. 
  12. ^ Sif, S; Gilmore T D (November 1994). "Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1". J. Virol. (UNITED STATES) 68 (11): 7131–8. ISSN 0022-538X. PMC 237152. PMID 7933095. 
  13. ^ Liu, Yi-Wen; Tseng Hui-Ping, Chen Lei-Chin, Chen Ben-Kuen, Chang Wen-Chang (July 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. (United States) 171 (2): 821–8. ISSN 0022-1767. PMID 12847250. 
  14. ^ a b Foti, Daniela; Iuliano Rodolfo, Chiefari Eusebio, Brunetti Antonio (April 2003). "A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription". Mol. Cell. Biol. (United States) 23 (8): 2720–32. doi:10.1128/MCB.23.8.2720-2732.2003. ISSN 0270-7306. PMC 152545. PMID 12665574. 
  15. ^ Shetty, S; Takahashi T, Matsui H, Ayengar R, Raghow R (May 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. (ENGLAND) 339 (3): 751–8. doi:10.1042/0264-6021:3390751. ISSN 0264-6021. PMC 1220213. PMID 10215616. 
  16. ^ Galvagni, F; Capo S, Oliviero S (March 2001). "Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter". J. Mol. Biol. (England) 306 (5): 985–96. doi:10.1006/jmbi.2000.4335. ISSN 0022-2836. PMID 11237613. 
  17. ^ a b c Wang, Yi-Ting; Chuang Jian-Ying, Shen Meng-Ru, Yang Wen-Bin, Chang Wen-Chang, Hung Jan-Jong (July 2008). "Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process". J. Mol. Biol. (England) 380 (5): 869–85. doi:10.1016/j.jmb.2008.05.043. PMID 18572193. 
  18. ^ Botella, L M; Sánchez-Elsner T, Rius C, Corbí A, Bernabéu C (September 2001). "Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation". J. Biol. Chem. (United States) 276 (37): 34486–94. doi:10.1074/jbc.M011611200. ISSN 0021-9258. PMID 11432852. 
  19. ^ Poncelet, A C; Schnaper H W (March 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. (United States) 276 (10): 6983–92. doi:10.1074/jbc.M006442200. ISSN 0021-9258. PMID 11114293. 
  20. ^ a b Di Padova, Monica; Bruno Tiziana, De Nicola Francesca, Iezzi Simona, D'Angelo Carmen, Gallo Rita, Nicosia Daniela, Corbi Nicoletta, Biroccio Annamaria, Floridi Aristide, Passananti Claudio, Fanciulli Maurizio (September 2003). "Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter". J. Biol. Chem. (United States) 278 (38): 36496–504. doi:10.1074/jbc.M306694200. ISSN 0021-9258. PMID 12847090. 
  21. ^ Singh, Jarnail; Murata Kenji, Itahana Yoko, Desprez Pierre-Yves (March 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 (England) 21 (12): 1812–22. doi:10.1038/sj.onc.1205252. ISSN 0950-9232. PMID 11896613. 
  22. ^ a b Zhang, Ying; Dufau Maria L (September 2002). "Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex". J. Biol. Chem. (United States) 277 (36): 33431–8. doi:10.1074/jbc.M204417200. ISSN 0021-9258. PMID 12091390. 
  23. ^ a b Sun, Jian-Min; Chen Hou Yu, Moniwa Mariko, Litchfield David W, Seto Edward, Davie James R (September 2002). "The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2". J. Biol. Chem. (United States) 277 (39): 35783–6. doi:10.1074/jbc.C200378200. ISSN 0021-9258. PMID 12176973. 
  24. ^ Won, Jaejoon; Yim Jeongbin, Kim Tae Kook (October 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. (United States) 277 (41): 38230–8. doi:10.1074/jbc.M206064200. ISSN 0021-9258. PMID 12151407. 
  25. ^ Li, Shi-Hua; Cheng Anna L, Zhou Hui, Lam Suzanne, Rao Manjula, Li He, Li Xiao-Jiang (March 2002). "Interaction of Huntington disease protein with transcriptional activator Sp1". Mol. Cell. Biol. (United States) 22 (5): 1277–87. doi:10.1128/MCB.22.5.1277-1287.2002. ISSN 0270-7306. PMC 134707. PMID 11839795. 
  26. ^ Botella, Luisa M; Sánchez-Elsner Tilman, Sanz-Rodriguez Francisco, Kojima Soichi, Shimada Jun, Guerrero-Esteo Mercedes, Cooreman Michael P, Ratziu Vlad, Langa Carmen, Vary Calvin P H, Ramirez Jose R, Friedman Scott, Bernabéu Carmelo (Dec. 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 (United States) 100 (12): 4001–10. doi:10.1182/blood.V100.12.4001. ISSN 0006-4971. PMID 12433697. 
  27. ^ Su, K; Yang X, Roos M D, Paterson A J, Kudlow J E (June 2000). "Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1". Biochem. J. (ENGLAND) 348 (2): 281–9. ISSN 0264-6021. PMC 1221064. PMID 10816420. 
  28. ^ Takada, Norio; Sanda Takaomi, Okamoto Hiroshi, Yang Jian-Ping, Asamitsu Kaori, Sarol Lilen, Kimura Genjiro, Uranishi Hiroaki, Tetsuka Toshifumi, Okamoto Takashi (August 2002). "RelA-associated inhibitor blocks transcription of human immunodeficiency virus type 1 by inhibiting NF-kappaB and Sp1 actions". J. Virol. (United States) 76 (16): 8019–30. doi:10.1128/JVI.76.16.8019-8030.2002. ISSN 0022-538X. PMC 155123. PMID 12134007. 
  29. ^ Sugawara, T; Saito M, Fujimoto S (August 2000). "Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression". Endocrinology (UNITED STATES) 141 (8): 2895–903. doi:10.1210/en.141.8.2895. ISSN 0013-7227. PMID 10919277. 
  30. ^ Biesiada, E; Hamamori Y, Kedes L, Sartorelli V (April 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. (UNITED STATES) 19 (4): 2577–84. ISSN 0270-7306. PMC 84050. PMID 10082523. 
  31. ^ Lécuyer, Eric; Herblot Sabine, Saint-Denis Marianne, Martin Richard, Begley C Glenn, Porcher Catherine, Orkin Stuart H, Hoang Trang (October 2002). "The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1". Blood (United States) 100 (7): 2430–40. doi:10.1182/blood-2002-02-0568. ISSN 0006-4971. PMID 12239153. 
  32. ^ Vallian, S; Chin K V, Chang K S (Dec. 1998). "The promyelocytic leukemia protein interacts with Sp1 and inhibits its transactivation of the epidermal growth factor receptor promoter". Mol. Cell. Biol. (UNITED STATES) 18 (12): 7147–56. ISSN 0270-7306. PMC 109296. PMID 9819401. 

33. S. Prasanna Kumar, P. Shilpa, B. P. Salimath (2009). "Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription factor". Current Trends in Biotechnology and Pharmacy 3 (2): 138–148.http://www.pharmainfo.net/files/Withaferin%20A_0.pdf.

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