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Transcription factor Sp1

From Wikipedia, the free encyclopedia

SP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSP1, entrez:6667, Sp1 transcription factor
External IDsOMIM: 189906; MGI: 98372; HomoloGene: 8276; GeneCards: SP1; OMA:SP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6667

20683

Ensembl

ENSG00000185591

ENSMUSG00000001280

UniProt

P08047

O89090

RefSeq (mRNA)

NM_001251825
NM_003109
NM_138473

NM_013672

RefSeq (protein)

NP_001238754
NP_003100
NP_612482

NP_038700

Location (UCSC)Chr 12: 53.38 – 53.42 MbChr 15: 102.31 – 102.34 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.[5]

Function

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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, O-GlcNAcylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor.[5]

In the SV40 virus, Sp1 binds to the GC boxes in the regulatory sequence of the genome.

Structure

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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 two glutamine-rich activation domains at its N-terminus that are believed to be necessary for promoter trans-activation.[6] SP1 most notably contains three zinc finger protein motifs at its C-terminus, by which it binds directly to DNA and allows for interaction of the protein with other transcriptional regulators. 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). Some 12,000 SP-1 binding sites are found in the human genome.[7]

Applications

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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.[8]

Recently, a putative promoter region in FTMT, and positive regulators {SP1, cAMP response element-binding protein (CREB), and Ying Yang 1 (YY1)] and negative regulators [GATA2, forkhead box protein A1 (FoxA1), and CCAAT enhancer-binding protein b (C/EBPb)] of FTMT transcription have been identified (Guaraldo et al, 2016).The effect of DFP on the DNA-binding activity of these regulators to the FTMT promoter was examined using chromatin immunoprecipitation (ChIP) assay. Among the regulators, only SP1 displayed significantly increased DNA- binding activity following DFP treatment in a dose-dependent manner. SP1 knockdown by siRNA abolished the DFP-induced increase in the mRNA levels of FTMT, indicating SP1-mediated regulation of FTMT expression in the presence of DFP. Treatment with Deferiprone increased the expression of cytoplasmic and nuclear SP1 with predominant localization in the nucleus.[9]

Inhibitors

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Plicamycin, an antineoplastic antibiotic produced by Streptomyces plicatus, and Withaferin A, a steroidal lactone from Withania somnifera plant are known to inhibit Sp1 transcription factor.[10][11]

miR-375-5p microRNA significantly decreased expression of SP1 and YAP1 in colorectal cancer cells. SP1 and YAP1 mRNAs are direct targets of miR-375-5p.[12]

Interactions

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Transcription factor Sp1 has been shown to interact with:

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000185591 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001280 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: Sp1 transcription factor".
  6. ^ Li L, He S, Sun JM, Davie JR (August 2004). "Gene regulation by Sp1 and Sp3". Biochemistry and Cell Biology. 82 (4): 460–471. doi:10.1139/o04-045. PMID 15284899.
  7. ^ Zhang B, Song L, Cai J, Li L, Xu H, Li M, et al. (May 2019). "The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation". Journal of Experimental & Clinical Cancer Research. 38 (1): 205. doi:10.1186/s13046-019-1203-2. PMC 6525466. PMID 31101117.
  8. ^ 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". Molecular and Cellular Biology. 23 (6): 1843–55. doi:10.1128/MCB.23.6.1843-1855.2003. PMC 149455. PMID 12612060.
  9. ^ Hara Y, Yanatori I, Tanaka A, Kishi F, Lemasters JJ, Nishina S, et al. (November 2020). "Iron loss triggers mitophagy through induction of mitochondrial ferritin". EMBO Reports. 21 (11): e50202. doi:10.15252/embr.202050202. PMC 7645172. PMID 32975364.
  10. ^ Choi ES, Nam JS, Jung JY, Cho NP, Cho SD (November 2014). "Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer". Scientific Reports. 4: 7162. Bibcode:2014NatSR...4E7162C. doi:10.1038/srep07162. PMC 4241519. PMID 25418289.
  11. ^ 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.[permanent dead link‍]
  12. ^ Xu X, Chen X, Xu M, Liu X, Pan B, Qin J, et al. (September 2019). "miR-375-3p suppresses tumorigenesis and partially reverses chemoresistance by targeting YAP1 and SP1 in colorectal cancer cells". Aging. 11 (18): 7357–7385. doi:10.18632/aging.102214. PMC 6781994. PMID 31543507.
  13. ^ a b Di Padova M, Bruno T, De Nicola F, Iezzi S, D'Angelo C, Gallo R, et al. (September 2003). "Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter". The Journal of Biological Chemistry. 278 (38): 36496–504. doi:10.1074/jbc.M306694200. PMID 12847090.
  14. ^ Liu YW, Tseng HP, Chen LC, Chen BK, Chang WC (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". Journal of Immunology. 171 (2): 821–8. doi:10.4049/jimmunol.171.2.821. PMID 12847250.
  15. ^ a b Foti D, Iuliano R, Chiefari E, Brunetti A (April 2003). "A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription". Molecular and Cellular Biology. 23 (8): 2720–32. doi:10.1128/MCB.23.8.2720-2732.2003. PMC 152545. PMID 12665574.
  16. ^ Li L, Artlett CM, Jimenez SA, Hall DJ, Varga J (October 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.
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  18. ^ 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". Journal of Molecular Biology. 293 (5): 1005–15. doi:10.1006/jmbi.1999.3213. PMID 10547281.
  19. ^ Karlseder J, Rotheneder H, Wintersberger E (April 1996). "Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F". Molecular and Cellular Biology. 16 (4): 1659–67. doi:10.1128/mcb.16.4.1659. PMC 231152. PMID 8657141.
  20. ^ Evellin S, Galvagni F, Zippo A, Neri F, Orlandini M, Incarnato D, et al. (March 2013). "FOSL1 controls the assembly of endothelial cells into capillary tubes by direct repression of αv and β3 integrin transcription". Molecular and Cellular Biology. 33 (6): 1198–209. doi:10.1128/MCB.01054-12. PMC 3592019. PMID 23319049.
  21. ^ 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". Journal of Molecular Biology. 306 (5): 985–96. doi:10.1006/jmbi.2000.4335. hdl:2318/141203. PMID 11237613. S2CID 29403871.
  22. ^ Singh J, Murata K, Itahana Y, Desprez PY (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. 21 (12): 1812–22. doi:10.1038/sj.onc.1205252. PMID 11896613.
  23. ^ a b Zhang Y, Dufau ML (September 2002). "Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex". The Journal of Biological Chemistry. 277 (36): 33431–8. doi:10.1074/jbc.M204417200. PMID 12091390.
  24. ^ a b Sun JM, Chen HY, Moniwa M, Litchfield DW, Seto E, Davie JR (September 2002). "The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2". The Journal of Biological Chemistry. 277 (39): 35783–6. doi:10.1074/jbc.C200378200. PMID 12176973.
  25. ^ Won J, Yim J, Kim TK (October 2002). "Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells". The Journal of Biological Chemistry. 277 (41): 38230–8. doi:10.1074/jbc.M206064200. PMID 12151407.
  26. ^ 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". Molecular and Cellular Biochemistry. 210 (1–2): 131–42. doi:10.1023/A:1007177623283. PMID 10976766. S2CID 1339642.
  27. ^ Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W (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 & Development. 17 (7): 896–911. doi:10.1101/gad.252103. PMC 196026. PMID 12670868.
  28. ^ Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, et al. (March 2002). "Interaction of Huntington disease protein with transcriptional activator Sp1". Molecular and Cellular Biology. 22 (5): 1277–87. doi:10.1128/MCB.22.5.1277-1287.2002. PMC 134707. PMID 11839795.
  29. ^ Botella LM, Sánchez-Elsner T, Sanz-Rodriguez F, Kojima S, Shimada J, Guerrero-Esteo M, et al. (December 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.
  30. ^ Krainc D, Bai G, Okamoto S, Carles M, Kusiak JW, Brent RN, et al. (October 1998). "Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1". The Journal of Biological Chemistry. 273 (40): 26218–24. doi:10.1074/jbc.273.40.26218. PMID 9748305.
  31. ^ Park SY, Shin HM, Han TH (September 2002). "Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter". Molecular Immunology. 39 (1–2): 25–30. doi:10.1016/S0161-5890(02)00055-X. PMID 12213324.
  32. ^ 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)". The Biochemical Journal. 339 (3): 751–8. doi:10.1042/0264-6021:3390751. PMC 1220213. PMID 10215616.
  33. ^ 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". Molecular and Cellular Biology. 19 (4): 2577–84. doi:10.1128/mcb.19.4.2577. PMC 84050. PMID 10082523.
  34. ^ Ström AC, 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 Research. 24 (11): 1981–6. doi:10.1093/nar/24.11.1981. PMC 145891. PMID 8668525.
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  36. ^ a b c Wang YT, Chuang JY, Shen MR, Yang WB, Chang WC, Hung JJ (July 2008). "Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process". Journal of Molecular Biology. 380 (5): 869–85. doi:10.1016/j.jmb.2008.05.043. PMID 18572193.
  37. ^ Su K, Yang X, Roos MD, Paterson AJ, Kudlow JE (June 2000). "Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1". The Biochemical Journal. 348 (2): 281–9. doi:10.1042/0264-6021:3480281. PMC 1221064. PMID 10816420.
  38. ^ Vallian S, Chin KV, Chang KS (December 1998). "The promyelocytic leukemia protein interacts with Sp1 and inhibits its transactivation of the epidermal growth factor receptor promoter". Molecular and Cellular Biology. 18 (12): 7147–56. doi:10.1128/mcb.18.12.7147. PMC 109296. PMID 9819401.
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  42. ^ Poncelet AC, Schnaper HW (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". The Journal of Biological Chemistry. 276 (10): 6983–92. doi:10.1074/jbc.M006442200. PMID 11114293.
  43. ^ 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. 141 (8): 2895–903. doi:10.1210/endo.141.8.7602. PMID 10919277.
  44. ^ Lécuyer E, Herblot S, Saint-Denis M, Martin R, Begley CG, Porcher C, et al. (October 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.
  45. ^ Yamabe Y, Shimamoto A, Goto M, Yokota J, Sugawara M, Furuichi Y (November 1998). "Sp1-mediated transcription of the Werner helicase gene is modulated by Rb and p53". Molecular and Cellular Biology. 18 (11): 6191–200. doi:10.1128/mcb.18.11.6191. PMC 109206. PMID 9774636.

Further reading

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

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