| Structural highlights
Function
SP1_HUMAN Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The carboxyl terminus of transcription factor Sp1 contains three contiguous Cys2-His2 zinc finger domains with the consensus sequence Cys-X2-4-Cys-X12-His-X3-His. We have used standard homonuclear two-dimensional NMR techniques to solve the solution structures of synthetic peptides corresponding to the last two zinc finger domains (Sp1f2 and Sp1f3, respectively) of Sp1. Our studies indicate a classical Cys2-His2 type fold for both the domains differing from each other primarily in the conformation of Cys-X2-Cys (beta-type I turn) and Cys-X4-Cys (beta-type II turn) elements. There are, however, no significant differences in the metal binding properties between the Cys-X4-Cys (Sp1f2) and Cys-X2-Cys (Sp1f3) subclasses of zinc fingers. The free solution structures of Sp1f2 and Sp1f3 are very similar to those of the analogous fingers of Zif268 bound to DNA. There is NMR spectral evidence suggesting that the Arg-Asp buttressing interaction observed in the Zif-268.DNA complex is also preserved in unbound Sp1f2 and Sp1f3. Modeling Sp1-DNA complex by overlaying the Sp1f2 and Sp1f3 structures on Zif268 fingers 1 and 2, respectively, predicts the role of key amino acid residues, the interference/protection data, and supports the model of Sp1-DNA interaction proposed earlier.
Structures of zinc finger domains from transcription factor Sp1. Insights into sequence-specific protein-DNA recognition.,Narayan VA, Kriwacki RW, Caradonna JP J Biol Chem. 1997 Mar 21;272(12):7801-9. PMID:9065444[16]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ding H, Benotmane AM, Suske G, Collen D, Belayew A. Functional interactions between Sp1 or Sp3 and the helicase-like transcription factor mediate basal expression from the human plasminogen activator inhibitor-1 gene. J Biol Chem. 1999 Jul 9;274(28):19573-80. PMID:10391891
- ↑ Yang X, Su K, Roos MD, Chang Q, Paterson AJ, Kudlow JE. O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits its transcriptional capability. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6611-6. Epub 2001 May 22. PMID:11371615 doi:http://dx.doi.org/10.1073/pnas.111099998
- ↑ Milanini-Mongiat J, Pouyssegur J, Pages G. Identification of two Sp1 phosphorylation sites for p42/p44 mitogen-activated protein kinases: their implication in vascular endothelial growth factor gene transcription. J Biol Chem. 2002 Jun 7;277(23):20631-9. Epub 2002 Mar 19. PMID:11904305 doi:http://dx.doi.org/10.1074/jbc.M201753200
- ↑ Bonello MR, Khachigian LM. Fibroblast growth factor-2 represses platelet-derived growth factor receptor-alpha (PDGFR-alpha) transcription via ERK1/2-dependent Sp1 phosphorylation and an atypical cis-acting element in the proximal PDGFR-alpha promoter. J Biol Chem. 2004 Jan 23;279(4):2377-82. Epub 2003 Oct 30. PMID:14593115 doi:http://dx.doi.org/10.1074/jbc.M308254200
- ↑ Hsu MC, Chang HC, Hung WC. HER-2/neu represses the metastasis suppressor RECK via ERK and Sp transcription factors to promote cell invasion. J Biol Chem. 2006 Feb 24;281(8):4718-25. Epub 2005 Dec 23. PMID:16377629 doi:http://dx.doi.org/10.1074/jbc.M510937200
- ↑ Vicart A, Lefebvre T, Imbert J, Fernandez A, Kahn-Perles B. Increased chromatin association of Sp1 in interphase cells by PP2A-mediated dephosphorylations. J Mol Biol. 2006 Dec 15;364(5):897-908. Epub 2006 Sep 16. PMID:17049555 doi:http://dx.doi.org/10.1016/j.jmb.2006.09.036
- ↑ Hung JJ, Wang YT, Chang WC. Sp1 deacetylation induced by phorbol ester recruits p300 to activate 12(S)-lipoxygenase gene transcription. Mol Cell Biol. 2006 Mar;26(5):1770-85. PMID:16478997 doi:http://dx.doi.org/10.1128/MCB.26.5.1770-1785.2006
- ↑ Zhang Y, Liao M, Dufau ML. Phosphatidylinositol 3-kinase/protein kinase Czeta-induced phosphorylation of Sp1 and p107 repressor release have a critical role in histone deacetylase inhibitor-mediated derepression [corrected] of transcription of the luteinizing hormone receptor gene. Mol Cell Biol. 2006 Sep;26(18):6748-61. PMID:16943418 doi:http://dx.doi.org/10.1128/MCB.00560-06
- ↑ Olofsson BA, Kelly CM, Kim J, Hornsby SM, Azizkhan-Clifford J. Phosphorylation of Sp1 in response to DNA damage by ataxia telangiectasia-mutated kinase. Mol Cancer Res. 2007 Dec;5(12):1319-30. doi: 10.1158/1541-7786.MCR-07-0374. PMID:18171990 doi:http://dx.doi.org/10.1158/1541-7786.MCR-07-0374
- ↑ Chung SS, Kim JH, Park HS, Choi HH, Lee KW, Cho YM, Lee HK, Park KS. Activation of PPARgamma negatively regulates O-GlcNAcylation of Sp1. Biochem Biophys Res Commun. 2008 Aug 8;372(4):713-8. doi:, 10.1016/j.bbrc.2008.05.096. Epub 2008 May 28. PMID:18513490 doi:http://dx.doi.org/10.1016/j.bbrc.2008.05.096
- ↑ Spengler ML, Guo LW, Brattain MG. Phosphorylation mediates Sp1 coupled activities of proteolytic processing, desumoylation and degradation. Cell Cycle. 2008 Mar 1;7(5):623-30. Epub 2007 Dec 4. PMID:18239466
- ↑ Iwahori S, Yasui Y, Kudoh A, Sato Y, Nakayama S, Murata T, Isomura H, Tsurumi T. Identification of phosphorylation sites on transcription factor Sp1 in response to DNA damage and its accumulation at damaged sites. Cell Signal. 2008 Oct;20(10):1795-803. doi: 10.1016/j.cellsig.2008.06.007. Epub, 2008 Jun 19. PMID:18619531 doi:http://dx.doi.org/10.1016/j.cellsig.2008.06.007
- ↑ Chuang JY, Wang YT, Yeh SH, Liu YW, Chang WC, Hung JJ. Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis. Mol Biol Cell. 2008 Mar;19(3):1139-51. doi: 10.1091/mbc.E07-09-0881. Epub 2008, Jan 16. PMID:18199680 doi:http://dx.doi.org/10.1091/mbc.E07-09-0881
- ↑ Jochmann R, Thurau M, Jung S, Hofmann C, Naschberger E, Kremmer E, Harrer T, Miller M, Schaft N, Sturzl M. O-linked N-acetylglucosaminylation of Sp1 inhibits the human immunodeficiency virus type 1 promoter. J Virol. 2009 Apr;83(8):3704-18. doi: 10.1128/JVI.01384-08. Epub 2009 Feb 4. PMID:19193796 doi:http://dx.doi.org/10.1128/JVI.01384-08
- ↑ Yu HT, Chan WW, Chai KH, Lee CW, Chang RC, Yu MS, McLoughlin DM, Miller CC, Lau KF. Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1. J Cell Biochem. 2010 Mar 1;109(4):782-93. doi: 10.1002/jcb.22457. PMID:20091743 doi:http://dx.doi.org/10.1002/jcb.22457
- ↑ Narayan VA, Kriwacki RW, Caradonna JP. Structures of zinc finger domains from transcription factor Sp1. Insights into sequence-specific protein-DNA recognition. J Biol Chem. 1997 Mar 21;272(12):7801-9. PMID:9065444
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