Sp1 전사인자

3. 구조

Sp1은 Sp/KLF 전사인자 계열에 속하는 단백질로, 전사 조절에 중요한 역할을 한다.^[2] 이 단백질은 N-말단에 전사 활성화에 관여하는 도메인을 가지고 있으며, C-말단에는 DNA에 직접 결합하는 아연 핑거 모티프를 포함하는 특징적인 구조를 지닌다.^[2] 자세한 구성 요소와 결합 부위에 대한 내용은 하위 문단을 참고할 수 있다.

3. 1. 구성 요소

3. 2. 결합 부위

4. 응용

Sp1은 아릴 탄화수소 수용체 및/또는 에스트로겐 수용체의 발현 변화 연구 시 대조 단백질로 사용된다. 이는 Sp1이 두 수용체 모두에 결합하며 일반적으로 그 양이 비교적 일정하게 유지되기 때문이다.^[4][46]

또한, 미토콘드리아 페리틴 (FTMT) 유전자 발현 조절 연구에도 활용된다. FTMT 유전자의 프로모터 영역에 결합하는 조절 인자들이 확인되었는데, 양성 조절 인자로는 SP1, cAMP 반응 요소 결합 단백질 (CREB), YY1 등이 있으며, 음성 조절 인자로는 GATA2, FoxA1, C/EBPb 등이 있다.^[5][43]

데페리프론(DFP)이 이들 조절 인자의 FTMT 프로모터에 대한 DNA 결합 활성에 미치는 영향을 염색질 면역 침강 (ChIP) 분석법으로 조사한 연구가 있다. 이 연구 결과, 여러 조절 인자 중 SP1만이 DFP 처리에 따라 농도 의존적으로 DNA 결합 활성이 유의하게 증가했다.^[5][44] siRNA를 이용한 SP1 녹다운 시, DFP에 의한 FTMT mRNA 수준 증가는 나타나지 않았다. 이는 DFP 존재 하에서 SP1을 통해 FTMT 발현 조절이 이루어짐을 시사한다.^[5][44] DFP 처리는 세포질 및 핵 내 SP1 발현을 증가시켰고, 주로 핵 내에 국한시켰다.^[5][44]

5. 억제제

Sp1 전사인자를 억제하는 물질은 항암 치료 등 다양한 의학 분야에서 중요한 연구 대상이 되고 있다. 여러 천연물 유래 화합물이나 마이크로RNA 등이 Sp1의 발현이나 활성을 조절하는 것으로 보고되었으며, 이는 새로운 치료 전략 개발의 가능성을 제시한다.^{[6][7][8][47][48][49]}

5. 1. 주요 억제제

6. 상호작용

Sp1 전사 인자는 다양한 단백질과 상호작용하여 유전자 발현 조절에 관여하는 것으로 알려져 있다. 연구를 통해 Sp1이 여러 특정 단백질들과 직접적으로 상호작용한다는 사실이 밝혀졌다.

6. 1. 상호작용 단백질 목록

• AATF^[2]
• CEBPB^[9][10]
• COL1A1^[11]
• E2F1^[12][13][14]
• FOSL1^[15]
• GABPA^[16]
• HDAC1^{[17][18][19][20]}
• HDAC2^[2][21]
• HMGA1^[2]
• HCFC1^[2][22]
• HTT^[23]
• KLF6^[24]
• MEF2C^[25]
• MEF2D^[26]
• MSX1^[27]
• 미오제닌^[28]
• POU2F1^[29][30]
• PPP1R13L^[31]
• PSMC5^[2][32]
• PML^[33]
• RELA^[34][35]
• SMAD3^[36][37]
• SUMO1^[38]
• SF1^[39]
• TAL1^[40]
• UBC
• WRN^[41]
• DDX3X

참조

_[1] 웹사이트 Entrez Gene: Sp1 transcription factor https://www.ncbi.nlm[...]
_[2] 논문 Gene regulation by Sp1 and Sp3 2004-08
_[3] 논문 The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation 2019-05
_[4] 논문 The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes 2003-03
_[5] 논문 Iron loss triggers mitophagy through induction of mitochondrial ferritin 2020-11
_[6] 논문 Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer 2014-11
_[7] 논문 Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription http://www.pharmainf[...]
_[8] 논문 miR-375-3p suppresses tumorigenesis and partially reverses chemoresistance by targeting YAP1 and SP1 in colorectal cancer cells 2019-09
_[9] 논문 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 2003-07
_[10] 논문 A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription 2003-04
_[11] 논문 Positive regulation of human alpha 1 (I) collagen promoter activity by transcription factor Sp1 1995-10
_[12] 논문 Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction 1996-04
_[13] 논문 Transcription factors of the Sp1 family: interaction with E2F and regulation of the murine thymidine kinase promoter 1999-11
_[14] 논문 Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F 1996-04
_[15] 논문 FOSL1 controls the assembly of endothelial cells into capillary tubes by direct repression of αv and β3 integrin transcription 2013-03
_[16] 논문 Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter 2001-03
_[17] 논문 Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter 2003-09
_[18] 논문 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 2002-03
_[19] 논문 Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex 2002-09
_[20] 논문 The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2 2002-09
_[21] 논문 Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells 2002-10
_[22] 논문 Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1 2003-04
_[23] 논문 Interaction of Huntington disease protein with transcriptional activator Sp1 2002-03
_[24] 논문 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 2002-12
_[25] 논문 Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1 1998-10
_[26] 논문 Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter 2002-09
_[27] 논문 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) 1999-05
_[28] 논문 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 1999-04
_[29] 논문 A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening 2000-07
_[30] 논문 The transcription factors Sp1 and Oct-1 interact physically to regulate human U2 snRNA gene expression 1996-06
_[31] 논문 RelA-associated inhibitor blocks transcription of human immunodeficiency virus type 1 by inhibiting NF-kappaB and Sp1 actions 2002-08
_[32] 논문 Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1 2000-06
_[33] 논문 The promyelocytic leukemia protein interacts with Sp1 and inhibits its transactivation of the epidermal growth factor receptor promoter 1998-12
_[34] 논문 NF-kappaB induced by IL-1beta inhibits elastin transcription and myofibroblast phenotype 2002-07
_[35] 논문 Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1 1994-11
_[36] 논문 Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation 2001-09
_[37] 논문 Sp1 and Smad proteins cooperate to mediate transforming growth factor-beta 1-induced alpha 2(I) collagen expression in human glomerular mesangial cells 2001-03
_[38] 논문 Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process 2008-07
_[39] 논문 Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression 2000-08
_[40] 논문 The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1 2002-10
_[41] 논문 Sp1-mediated transcription of the Werner helicase gene is modulated by Rb and p53 1998-11
_[42] 웹사이트 Entrez Gene: Sp1 transcription factor https://www.ncbi.nlm[...] 2021-10-03
_[43] 논문 Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control https://pubmed.ncbi.[...] 2016-09-14
_[44] 논문 Iron loss triggers mitophagy through induction of mitochondrial ferritin 2020-11
_[45] 논문 The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation 2019
_[46] 논문 The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes 2003-03
_[47] 논문 Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer 2014-11
_[48] 논문 Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription http://www.pharmainf[...] 2009
_[49] 논문 miR-375-3p suppresses tumorigenesis and partially reverses chemoresistance by targeting YAP1 and SP1 in colorectal cancer cells 2019-09
_[50] 논문 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 2003-07
_[51] 논문 A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription 2003-04
_[52] 논문 Positive regulation of human alpha 1 (I) collagen promoter activity by transcription factor Sp1 1995-10
_[53] 논문 Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction 1996-04
_[54] 논문 Transcription factors of the Sp1 family: interaction with E2F and regulation of the murine thymidine kinase promoter 1999-11
_[55] 논문 Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F 1996-04
_[56] 논문 FOSL1 controls the assembly of endothelial cells into capillary tubes by direct repression of αv and β3 integrin transcription 2013-03
_[57] 논문 Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter 2001-03
_[58] 논문 Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter 2003-09
_[59] 논문 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 2002-03
_[60] 논문 Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex 2002-09
_[61] 논문 The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2 2002-09
_[62] 논문 Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells 2002-10
_[63] 논문 Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1 2003-04
_[64] 논문 Interaction of Huntington disease protein with transcriptional activator Sp1 2002-03
_[65] 논문 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 2002-12
_[66] 논문 Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1 1998-10
_[67] 논문 Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter 2002-09
_[68] 논문 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) 1999-05
_[69] 논문 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 1999-04
_[70] 논문 A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening 2000-07
_[71] 논문 The transcription factors Sp1 and Oct-1 interact physically to regulate human U2 snRNA gene expression 1996-06
_[72] 논문 RelA-associated inhibitor blocks transcription of human immunodeficiency virus type 1 by inhibiting NF-kappaB and Sp1 actions 2002-08
_[73] 논문 Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1 2000-06
_[74] 논문 The promyelocytic leukemia protein interacts with Sp1 and inhibits its transactivation of the epidermal growth factor receptor promoter 1998-12
_[75] 논문 NF-kappaB induced by IL-1beta inhibits elastin transcription and myofibroblast phenotype 2002-07
_[76] 논문 Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1 1994-11
_[77] 논문 Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation 2001-09
_[78] 논문 Sp1 and Smad proteins cooperate to mediate transforming growth factor-beta 1-induced alpha 2(I) collagen expression in human glomerular mesangial cells 2001-03
_[79] 논문 Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process 2008-07
_[80] 논문 Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression 2000-08
_[81] 논문 The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1 2002-10
_[82] 논문 Sp1-mediated transcription of the Werner helicase gene is modulated by Rb and p53 1998-11
_[83] 웹인용 Entrez Gene: Sp1 transcription factor https://www.ncbi.nlm[...]