French
DeutschSp1転写因子
Sp1転写因子（specificity protein 1）は、ヒトではSP1遺伝子によってコードされるタンパク質である[5]。
機能
[編集]SP1遺伝子にコードされるSP1タンパク質はジンクフィンガー型転写因子であり、多くのプロモーターのGCリッチモチーフに結合する。SP1タンパク質は、細胞分化、細胞成長、アポトーシス、免疫応答、DNA損傷応答、クロマチンリモデリングなど多くの細胞過程に関与している。このタンパク質の活性はリン酸化、アセチル化、グリコシル化などの翻訳後修飾やタンパク質分解によるプロセシングの影響を受け、アクチベーターとしてもリプレッサーとしても機能する[5]。
ミトコンドリアフェリチン遺伝子（FTMT）の推定プロモーター領域に結合する転写の正の調節因子としてSP1、CREB、YY1が、負の調節因子としてGATA2、FOXA1、C/EBPβが同定されている[6]。これらの調節因子のDNA結合活性に対するデフェリプロン（DFP）の影響がクロマチン免疫沈降（ChIP）アッセイによって調べられている。これらの中で、SP1のみがDFP処理後に用量依存的なDNA結合活性の大幅な増大を示した。siRNAによるSP1のノックダウンによってDFPによるFTMTのｍRNAレベルの増加はみられなくなることから、DFPの存在下ではSP1を介したFTMTの発現の調節が行われていることが示唆される。DFP処理はSP1の細胞質および核内での発現を増加させ、主に核内に局在させる[7]。
構造
[編集]SP1は転写因子のSp/KLFファミリーに属し、785アミノ酸長、81 kDaである。SP1転写因子はジンクフィンガーモチーフをもち、これを介してDNAに直接結合して遺伝子の転写を亢進させる。ジンクフィンガーはCys2/His2型で、5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3'のコンセンサス配列（GCボックスエレメント）に結合する。ヒトゲノム中には12,000か所程度のSP1結合部位が見つかっている[8]。
応用
[編集]Sp1は芳香族炭化水素受容体やエストロゲン受容体の双方に結合し、そして比較的一定のレベルで存在するため、これらの受容体の増加や減少の研究の際のコントロールタンパク質として利用される[9]。
阻害剤
[編集]Streptomyces plicatusによって産生される抗腫瘍性抗生物質であるプリカマイシンや、アシュワガンダWithania somnifera由来のステロイドラクトンであるウィザフェリンAはSp1転写因子を阻害することが知られている[10][11]。
miR-375-5pは大腸がん細胞でSP1とYAP1の発現を大きく低下させる。SP1とYAP1のｍRNAはmiR-375-5pの直接的な標的である[12]。
相互作用
[編集]Sp1転写因子は次に挙げる因子と相互作用することが示されている。
- AATF[13]
- CEBPB[14][15]
- COL1A1[16]
- E2F1[17][18][19]
- FOSL1[20]
- GABPA[21]
- HDAC1[13][22][23][24]
- HDAC2[23][24][25]
- HMGA1[15]
- HCFC1[26][27]
- HTT[28]
- KLF6[29]
- MEF2C[30]
- MEF2D[31]
- MSX1[32]
- MYOG[33]
- POU2F1[26][34]
- PPP1R13L[35]
- PSMC5[36][37]
- PML[38]
- RELA[39][40]
- SMAD3[41][42]
- SUMO1[36]
- SF1[43]
- TAL1[44]
- UBC[36]
- WRN[45]
出典
[編集]- ^ a b c GRCh38: Ensembl release 89: ENSG00000185591 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001280 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
- ^ a b “Entrez Gene: Sp1 transcription factor”. 2021年10月3日閲覧。
- ^ Guaraldo, Michela; Santambrogio, Paolo; Rovelli, Elisabetta; Di Savino, Augusta; Saglio, Giuseppe; Cittaro, Davide; Roetto, Antonella; Levi, Sonia (2016-09-14). “Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control”. Scientific Reports 6: 33432. doi:10.1038/srep33432. ISSN 2045-2322. PMC 5022048. PMID 27625068.
- ^ “Iron loss triggers mitophagy through induction of mitochondrial ferritin”. EMBO Reports 21 (11): e50202. (November 2020). doi:10.15252/embr.202050202. PMID 32975364.
- ^ Zhang, Bosen; Song, Liwei; Cai, Jiali; Li, Lei; Xu, Hong; Li, Mengying; Wang, Jiamin; Shi, Minmin et al. (2019). “The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation” (英語). Journal of Experimental & Clinical Cancer Research 38 (1): 205. doi:10.1186/s13046-019-1203-2. ISSN 1756-9966. PMC 6525466. PMID 31101117.
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- ^ “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).[リンク切れ]
- ^ “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. PMC 6781994. PMID 31543507.
- ^ a b “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.
- ^ a b “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. PMC 152545. 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. PMC 231153. 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. PMC 231152. 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. PMC 3592019. 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. hdl:2318/141203. 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.
- ^ a b “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.
- ^ a b “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.
- ^ a b “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. PMC 196026. 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. PMC 134707. 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 ( Pt 3) (3): 751–8. (May 1999). doi:10.1042/0264-6021:3390751. PMC 1220213. 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. PMC 84050. 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. PMC 145891. 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. PMC 155123. PMID 12134007.
- ^ a b c “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 Pt 2 (2): 281–9. (June 2000). doi:10.1042/0264-6021:3480281. PMC 1221064. 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. PMC 109296. 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. PMC 237152. 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/en.141.8.2895. 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. PMC 109206. PMID 9774636.
関連文献
[編集]- “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.
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