Transcription factor Sp1

Last updated

SP1
Protein SP1 PDB 1sp1.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SP1 , entrez:6667, Sp1 transcription factor
External IDs OMIM: 189906; MGI: 98372; HomoloGene: 8276; GeneCards: SP1; OMA:SP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 Mb Chr 15: 102.31 – 102.34 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

Contents

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. [5]

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. [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]

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. [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

Transcription factor Sp1 has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">Androgen receptor</span> Mammalian protein found in humans

The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

<span class="mw-page-title-main">Aryl hydrocarbon receptor nuclear translocator</span> Protein-coding gene in the species Homo sapiens

The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL–ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.

<span class="mw-page-title-main">Nuclear receptor coactivator 1</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor coactivator 1 (NCOA1), also called steroid receptor coactivator-1 (SRC-1), is a transcriptional coregulatory protein that contains several nuclear receptor–interacting domains and possesses intrinsic histone acetyltransferase activity. It is encoded by the gene NCOA1.

<span class="mw-page-title-main">Small heterodimer partner</span> Protein found in humans

The small heterodimer partner (SHP) also known as NR0B2 is a protein that in humans is encoded by the NR0B2 gene. SHP is a member of the nuclear receptor family of intracellular transcription factors. SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore, it is technically neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.

<span class="mw-page-title-main">RELA</span> Protein-coding gene in the species Homo sapiens

Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the RELA gene.

<span class="mw-page-title-main">CEBPB</span> Protein-coding gene in humans

CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.

<span class="mw-page-title-main">SIN3A</span> Protein-coding gene in the species Homo sapiens

Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.

<span class="mw-page-title-main">POU2F1</span> Protein-coding gene in the species Homo sapiens

POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the POU2F1 gene.

<span class="mw-page-title-main">MEF2C</span> Protein-coding gene in the species Homo sapiens

Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene. MEF2C is a transcription factor in the Mef2 family.

<span class="mw-page-title-main">NFYB</span> Protein-coding gene in the species Homo sapiens

Nuclear transcription factor Y subunit beta is a protein that in humans is encoded by the NFYB gene.

<span class="mw-page-title-main">GABPA</span> Protein-coding gene in the species Homo sapiens

GA-binding protein alpha chain is a protein that in humans is encoded by the GABPA gene.

<span class="mw-page-title-main">COUP-TFI</span> Protein found in humans

COUP-TF1 also known as NR2F1 is a protein that in humans is encoded by the NR2F1 gene. This protein is a member of nuclear hormone receptor family of steroid hormone receptors.

<span class="mw-page-title-main">GTF2I</span> Protein-coding gene in the species Homo sapiens

General transcription factor II-I is a protein that in humans is encoded by the GTF2I gene.

<span class="mw-page-title-main">SNW1</span> Protein-coding gene in the species Homo sapiens

SNW domain-containing protein 1 is a protein that in humans is encoded by the SNW1 gene.

<span class="mw-page-title-main">MEF2D</span> Protein-coding gene in the species Homo sapiens

Myocyte-specific enhancer factor 2D is a protein that in humans is encoded by the MEF2D gene.

<span class="mw-page-title-main">TFCP2</span> Protein-coding gene in the species Homo sapiens

Alpha-globin transcription factor CP2 is a protein that in humans is encoded by the TFCP2 gene.

<span class="mw-page-title-main">MAFG</span> Protein-coding gene in the species Homo sapiens

Transcription factor MafG is a bZip Maf transcription factor protein that in humans is encoded by the MAFG gene.

<span class="mw-page-title-main">KLF11</span> Protein-coding gene in the species Homo sapiens

Krueppel-like factor 11 is a protein that in humans is encoded by the KLF11 gene.

<span class="mw-page-title-main">TCF20</span> Protein-coding gene in the species Homo sapiens

Transcription factor 20 is a protein that in humans is encoded by the TCF20 gene.

<span class="mw-page-title-main">GTF2E2</span> Protein-coding gene in the species Homo sapiens

General transcription factor IIE subunit 2 (GTF2E2), also known as transcription initiation factor IIE subunit beta (TFIIE-beta), is a protein that in humans is encoded by the GTF2E2 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000185591 Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. 1 2 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. 1 2 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.
  17. Lin SY, Black AR, Kostic D, Pajovic S, Hoover CN, Azizkhan JC (April 1996). "Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction". Molecular and Cellular Biology. 16 (4): 1668–75. doi:10.1128/mcb.16.4.1668. PMC   231153 . PMID   8657142.
  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. 1 2 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. 1 2 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. 1 2 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.
  35. Takada N, Sanda T, Okamoto H, Yang JP, Asamitsu K, Sarol L, et al. (August 2002). "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. doi:10.1128/JVI.76.16.8019-8030.2002. PMC   155123 . PMID   12134007.
  36. 1 2 3 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.
  39. 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. PMID   12055073. S2CID   15753719.
  40. Sif S, Gilmore TD (November 1994). "Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1". Journal of Virology. 68 (11): 7131–8. doi:10.1128/JVI.68.11.7131-7138.1994. PMC   237152 . PMID   7933095.
  41. Botella LM, Sánchez-Elsner T, Rius C, Corbí A, Bernabéu C (September 2001). "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. doi: 10.1074/jbc.M011611200 . hdl: 10261/168007 . PMID   11432852.
  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

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