Biology:Sp1 transcription factor
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Short description: Protein-coding gene in the species Homo sapiens
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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 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 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
Sp1 transcription factor has been shown to interact with:
- AATF,[9]
- CEBPB,[10][11]
- COL1A1,[12]
- E2F1,[13][14][15]
- FOSL1,[16]
- GABPA,[17]
- HDAC1,[9][18][19][20]
- HDAC2,[19][20][21]
- HMGA1,[11]
- HCFC1,[22][23]
- HTT,[24]
- KLF6,[25]
- MEF2C,[26]
- MEF2D,[27]
- MSX1,[28]
- Myogenin,[29]
- POU2F1,[22][30]
- PPP1R13L,[31]
- PSMC5,[32][33]
- PML,[34]
- RELA,[35][36]
- SMAD3,[37][38]
- SUMO1,[32]
- SF1,[39]
- TAL1,[40]
- UBC.[32]
- WRN,[41]
- DDX3X
References
- ↑ 1.0 1.1 "Entrez Gene: Sp1 transcription factor". https://www.ncbi.nlm.nih.gov/gene/6667.
- ↑ 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.
- ↑ "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.
- ↑ "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.
- ↑ "Iron loss triggers mitophagy through induction of mitochondrial ferritin". EMBO Reports 21 (11): e50202. November 2020. doi:10.15252/embr.202050202. PMID 32975364.
- ↑ "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. Bibcode: 2014NatSR...4E7162C.
- ↑ "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}}]
- ↑ "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.
- ↑ 9.0 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.
- ↑ "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.
- ↑ 11.0 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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ 19.0 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.
- ↑ 20.0 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.
- ↑ "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.
- ↑ 22.0 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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ 32.0 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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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.
- ↑ "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
- "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". The Journal of Biological Chemistry 276 (31): 29466–78. August 2001. doi:10.1074/jbc.M102604200. PMID 11340073.
- "Differentiation-dependent and cell-specific regulation of the hIGFBP-1 gene in human endometrium". Annals of the New York Academy of Sciences 828 (1): 27–37. September 1997. doi:10.1111/j.1749-6632.1997.tb48521.x. PMID 9329821. Bibcode: 1997NYASA.828...27T.
- "The regulation of E2F by pRB-family proteins". Genes & Development 12 (15): 2245–62. August 1998. doi:10.1101/gad.12.15.2245. PMID 9694791.
- "Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes". The Journal of Steroid Biochemistry and Molecular Biology 85 (2–5): 401–14. June 2003. doi:10.1016/S0960-0760(03)00230-9. PMID 12943729. https://zenodo.org/record/1260176.
- "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA and Cell Biology 23 (4): 193–205. April 2004. doi:10.1089/104454904773819789. PMID 15142377. https://zenodo.org/record/1235217.
- "Role of viral regulatory and accessory proteins in HIV-1 replication". Frontiers in Bioscience 9 (1–3): 2388–413. September 2004. doi:10.2741/1403. PMID 15353294.
- "The Vpr protein from HIV-1: distinct roles along the viral life cycle". Retrovirology 2: 11. February 2005. doi:10.1186/1742-4690-2-11. PMID 15725353.
- "Synergistic activation of the human immunodeficiency virus type 1 promoter by the viral Tat protein and cellular transcription factor Sp1". Journal of Virology 66 (6): 3932–6. June 1992. doi:10.1128/JVI.66.6.3932-3936.1992. PMID 1583736.
- "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. September 1991. doi:10.1016/0888-7543(91)90114-T. PMID 1662663.
- "Interaction of Sp1 with the human gamma globin promoter: binding and transactivation of normal and mutant promoters". Blood 78 (7): 1853–63. October 1991. doi:10.1182/blood.V78.7.1853.1853. PMID 1912570.
- "Sp1-dependent activation of a synthetic promoter by human immunodeficiency virus type 1 Tat protein". Proceedings of the National Academy of Sciences of the United States of America 88 (19): 8510–4. October 1991. doi:10.1073/pnas.88.19.8510. PMID 1924310. Bibcode: 1991PNAS...88.8510K.
- "Synergistic activation by the glutamine-rich domains of human transcription factor Sp1". Cell 59 (5): 827–36. December 1989. doi:10.1016/0092-8674(89)90606-5. PMID 2512012.
- "Role of SP1-binding domains in in vivo transcriptional regulation of the human immunodeficiency virus type 1 long terminal repeat". Journal of Virology 63 (6): 2585–91. June 1989. doi:10.1128/JVI.63.6.2585-2591.1989. PMID 2657100.
- "O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation". Cell 55 (1): 125–33. October 1988. doi:10.1016/0092-8674(88)90015-3. PMID 3139301.
- "Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain". Cell 51 (6): 1079–90. December 1987. doi:10.1016/0092-8674(87)90594-0. PMID 3319186.
- "Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells". The Journal of Biological Chemistry 270 (25): 15320–6. June 1995. doi:10.1074/jbc.270.25.15320. PMID 7541039.
- "Functional analyses of the transcription factor Sp4 reveal properties distinct from Sp1 and Sp3". The Journal of Biological Chemistry 270 (42): 24989–94. October 1995. doi:10.1074/jbc.270.42.24989. PMID 7559627.
- "Association of p107 with Sp1: genetically separable regions of p107 are involved in regulation of E2F- and Sp1-dependent transcription". Molecular and Cellular Biology 15 (10): 5444–52. October 1995. doi:10.1128/mcb.15.10.5444. PMID 7565695.
- "Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Sp1 and trans-activation of viral long terminal repeat". The Journal of Biological Chemistry 270 (43): 25564–9. October 1995. doi:10.1074/jbc.270.43.25564. PMID 7592727.
- "HIV Tat represses transcription through Sp1-like elements in the basal promoter". Immunity 3 (1): 127–38. July 1995. doi:10.1016/1074-7613(95)90165-5. PMID 7621073.
- "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. July 1995. doi:10.1016/0378-1119(95)00140-2. PMID 7622044.
- "Angiotensin II-inducible platelet-derived growth factor-D transcription requires specific Ser/Thr residues in the second zinc finger region of Sp1". Circulation Research 102 (4): e38-51. February 2008. 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
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