Biology:Transcription factor Sp1

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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, O-GlcNAcylation, 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 sequence 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 two glutamine-rich activation domains at its N-terminus that are believed to be necessary for promoter trans-activation.[2] 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.[3]

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.[4]

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.[5]

Inhibitors

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.[6][7]

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.[8]

Interactions

Transcription factor Sp1 has been shown to interact with:

References

  1. 1.0 1.1 "Entrez Gene: Sp1 transcription factor". https://www.ncbi.nlm.nih.gov/gene/6667. 
  2. Li, Lin; He, Shihua; Sun, Jian-Min; Davie, James R (2004-08-01). "Gene regulation by Sp1 and Sp3". Biochemistry and Cell Biology 82 (4): 460–471. doi:10.1139/o04-045. ISSN 0829-8211. PMID 15284899. https://doi.org/10.1139/o04-045. 
  3. "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. May 2019. doi:10.1186/s13046-019-1203-2. PMID 31101117. 
  4. "The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes". Molecular and Cellular Biology 23 (6): 1843–55. March 2003. doi:10.1128/MCB.23.6.1843-1855.2003. PMID 12612060. 
  5. "Iron loss triggers mitophagy through induction of mitochondrial ferritin". EMBO Reports 21 (11): e50202. November 2020. doi:10.15252/embr.202050202. PMID 32975364. 
  6. "Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer". Scientific Reports 4: 7162. November 2014. doi:10.1038/srep07162. PMID 25418289. Bibcode2014NatSR...4E7162C. 
  7. "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. 2009. http://www.pharmainfo.net/files/Withaferin%20A_0.pdf. [yes|permanent dead link|dead link}}]
  8. "miR-375-3p suppresses tumorigenesis and partially reverses chemoresistance by targeting YAP1 and SP1 in colorectal cancer cells". Aging 11 (18): 7357–7385. September 2019. doi:10.18632/aging.102214. PMID 31543507. 
  9. 9.0 9.1 "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. September 2003. doi:10.1074/jbc.M306694200. PMID 12847090. 
  10. "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. July 2003. doi:10.4049/jimmunol.171.2.821. PMID 12847250. 
  11. 11.0 11.1 "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. April 2003. doi:10.1128/MCB.23.8.2720-2732.2003. PMID 12665574. 
  12. "Positive regulation of human alpha 1 (I) collagen promoter activity by transcription factor Sp1". Gene 164 (2): 229–34. October 1995. doi:10.1016/0378-1119(95)00508-4. PMID 7590335. 
  13. "Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction". Molecular and Cellular Biology 16 (4): 1668–75. April 1996. doi:10.1128/mcb.16.4.1668. PMID 8657142. 
  14. "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. November 1999. doi:10.1006/jmbi.1999.3213. PMID 10547281. 
  15. "Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F". Molecular and Cellular Biology 16 (4): 1659–67. April 1996. doi:10.1128/mcb.16.4.1659. PMID 8657141. 
  16. "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. March 2013. doi:10.1128/MCB.01054-12. PMID 23319049. 
  17. "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. March 2001. doi:10.1006/jmbi.2000.4335. PMID 11237613. 
  18. "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. March 2002. doi:10.1038/sj.onc.1205252. PMID 11896613. 
  19. 19.0 19.1 "Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex". The Journal of Biological Chemistry 277 (36): 33431–8. September 2002. doi:10.1074/jbc.M204417200. PMID 12091390. 
  20. 20.0 20.1 "The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2". The Journal of Biological Chemistry 277 (39): 35783–6. September 2002. doi:10.1074/jbc.C200378200. PMID 12176973. 
  21. "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. October 2002. doi:10.1074/jbc.M206064200. PMID 12151407. 
  22. 22.0 22.1 "A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening". Molecular and Cellular Biochemistry 210 (1–2): 131–42. July 2000. doi:10.1023/A:1007177623283. PMID 10976766. 
  23. "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. April 2003. doi:10.1101/gad.252103. PMID 12670868. 
  24. "Interaction of Huntington disease protein with transcriptional activator Sp1". Molecular and Cellular Biology 22 (5): 1277–87. March 2002. doi:10.1128/MCB.22.5.1277-1287.2002. PMID 11839795. 
  25. "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. December 2002. doi:10.1182/blood.V100.12.4001. PMID 12433697. 
  26. "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. October 1998. doi:10.1074/jbc.273.40.26218. PMID 9748305. 
  27. "Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter". Molecular Immunology 39 (1–2): 25–30. September 2002. doi:10.1016/S0161-5890(02)00055-X. PMID 12213324. 
  28. "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. May 1999. doi:10.1042/0264-6021:3390751. PMID 10215616. 
  29. "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. April 1999. doi:10.1128/mcb.19.4.2577. PMID 10082523. 
  30. "The transcription factors Sp1 and Oct-1 interact physically to regulate human U2 snRNA gene expression". Nucleic Acids Research 24 (11): 1981–6. June 1996. doi:10.1093/nar/24.11.1981. PMID 8668525. 
  31. "RelA-associated inhibitor blocks transcription of human immunodeficiency virus type 1 by inhibiting NF-kappaB and Sp1 actions". Journal of Virology 76 (16): 8019–30. August 2002. doi:10.1128/JVI.76.16.8019-8030.2002. PMID 12134007. 
  32. 32.0 32.1 32.2 "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. July 2008. doi:10.1016/j.jmb.2008.05.043. PMID 18572193. 
  33. "Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1". The Biochemical Journal 348 (2): 281–9. June 2000. doi:10.1042/0264-6021:3480281. PMID 10816420. 
  34. "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. December 1998. doi:10.1128/mcb.18.12.7147. PMID 9819401. 
  35. "NF-kappaB induced by IL-1beta inhibits elastin transcription and myofibroblast phenotype". American Journal of Physiology. Cell Physiology 283 (1): C58-65. July 2002. doi:10.1152/ajpcell.00314.2001. PMID 12055073. 
  36. "Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1". Journal of Virology 68 (11): 7131–8. November 1994. doi:10.1128/JVI.68.11.7131-7138.1994. PMID 7933095. 
  37. "Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation". The Journal of Biological Chemistry 276 (37): 34486–94. September 2001. doi:10.1074/jbc.M011611200. PMID 11432852. 
  38. "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. March 2001. doi:10.1074/jbc.M006442200. PMID 11114293. 
  39. "Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression". Endocrinology 141 (8): 2895–903. August 2000. doi:10.1210/endo.141.8.7602. PMID 10919277. 
  40. "The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1". Blood 100 (7): 2430–40. October 2002. doi:10.1182/blood-2002-02-0568. PMID 12239153. 
  41. "Sp1-mediated transcription of the Werner helicase gene is modulated by Rb and p53". Molecular and Cellular Biology 18 (11): 6191–200. November 1998. doi:10.1128/mcb.18.11.6191. PMID 9774636. 

Further reading

External links

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