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
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]
^Li L, He S, Sun JM, Davie JR (August 2004). "Gene regulation by Sp1 and Sp3". Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. 82 (4): 460–471.
doi:
10.1139/o04-045.
PMID15284899.
^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.
PMID10547281.
^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.
PMID11237613.
S2CID29403871.
^
abGunther 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.
PMID10976766.
S2CID1339642.
^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.
PMID12213324.
^
abcWang 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.
PMID18572193.
^Kuang PP, Berk JL, Rishikof DC, Foster JA, Humphries DE, Ricupero DA, et al. (July 2002). "NF-kappaB induced by IL-1beta inhibits elastin transcription and myofibroblast phenotype". American Journal of Physiology. Cell Physiology. 283 (1): C58-65.
doi:
10.1152/ajpcell.00314.2001.
PMID12055073.
S2CID15753719.
Szpirer J, Szpirer C, Riviere M, Levan G, Marynen P, Cassiman JJ, et al. (September 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.
PMID1662663.
Courey AJ, Holtzman DA, Jackson SP, Tjian R (December 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.
PMID2512012.
S2CID2910480.
Jackson SP, Tjian R (October 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.
PMID3139301.
S2CID42523965.
Kadonaga JT, Carner KR, Masiarz FR, Tjian R (December 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.
PMID3319186.
S2CID19383553.
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
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]
^Li L, He S, Sun JM, Davie JR (August 2004). "Gene regulation by Sp1 and Sp3". Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. 82 (4): 460–471.
doi:
10.1139/o04-045.
PMID15284899.
^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.
PMID10547281.
^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.
PMID11237613.
S2CID29403871.
^
abGunther 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.
PMID10976766.
S2CID1339642.
^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.
PMID12213324.
^
abcWang 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.
PMID18572193.
^Kuang PP, Berk JL, Rishikof DC, Foster JA, Humphries DE, Ricupero DA, et al. (July 2002). "NF-kappaB induced by IL-1beta inhibits elastin transcription and myofibroblast phenotype". American Journal of Physiology. Cell Physiology. 283 (1): C58-65.
doi:
10.1152/ajpcell.00314.2001.
PMID12055073.
S2CID15753719.
Szpirer J, Szpirer C, Riviere M, Levan G, Marynen P, Cassiman JJ, et al. (September 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.
PMID1662663.
Courey AJ, Holtzman DA, Jackson SP, Tjian R (December 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.
PMID2512012.
S2CID2910480.
Jackson SP, Tjian R (October 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.
PMID3139301.
S2CID42523965.
Kadonaga JT, Carner KR, Masiarz FR, Tjian R (December 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.
PMID3319186.
S2CID19383553.