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激活蛋白1(activator protein-1,AP-1)是机体内一类重要的核转录因子,是由Jun、Fos、ATF和MAF蛋白家族组成的同源二聚体或异源二聚体。主要通过其高度保守的碱性亮氨酸拉链(basic leucine zipper,b ZIP)与DNA结合,参与多种生长因子和细胞因子的基因转录,从而调控细胞增殖、分化、转化及凋亡等过程。AP-1可调节多种刺激物的基因表达,同时也受多种细胞外物质的刺激而活化。活化的AP-1可参与多器官、多系统疾病的发生发展,如多种恶性肿瘤及免疫相关疾病等。本文旨在概述其近年来的研究进展。
Abstract:Activator ptotein-1(AP-1) is an important class of nuclear transcription factors in the body,and is a homodimer or heterodimer composed of the Jun,Fos,ATF and MAF protein families.AP-1 binds to DNA mainly through its highly conserved basic leucine zipper(b ZIP),which involves in the transcription of a variety of growth factors and cytokines gene,and thus regulates the processes of cell proliferation,differentiation,transformation and apoptosis.AP-1 regulates the gene expression of many stimuli and it also can be activated by the stimulation of many extracellular substances.Activated AP-1 can participate in the development of the diseases of multiple organ and multi-system,such as many malignancies and immune-related diseases.This article aims to summarize its recent research progress.
[1]YE N,DING Y,WILD C,et al.Small molecule inhibitors targeting activator protein 1(AP-1)[J].J Med Chem,2014,57(16):6930-6948.
[2]RYLSKI M,KACZMAREK L.Ap-1 targets in the brain[J].Front Biosci,2004,9:8-23.
[3]SHAULIAN E,KARIN M.AP-1 as a regulator of cell Life and death[J].Nat Cell Biol,2002,4(5):E131-E136.
[4]NIKOLAEV Y,PERVUSHIN K.Structural basis of RNA binding by leucine zipper GCN4[J].Protein Sci,2012,21(5):667-676.
[5]CHINENOV Y,KERPPOLA TK.Close encounters of many kinds:Fos-Jun interactions that mediate transcription regulatory specificity[J].Oncogene,2001,20(19):2438-2452.
[6]EFERL R,WAGNER EF.AP-1:a double-edged sword in tumorigenesis[J].Nat Rev Cancer,2003,3(11):859-868.
[7]WAGNER EF,NEBREDA AR.Signal integration by JNK and p38 MAPK pathways in cancer development[J].Nat Rev Cancer,2009,9(8):537-549.
[8]SHAO YY,HSIEH MS,WANG HY,et al.Hepatitis C virus core protein potentiates proangiogenic activity of hepatocellular carcinoma cells[J].Oncotarget,2017,8(49):86681-86692.
[9]HUANG Q,LAN F,WANG X,et al.IL-1β-induced activation of p38 promotes metastasis in gastric adenocarcinoma via upregulation of AP-1/c-fos,MMP2 and MMP9[J].Mol Cancer,2014,13:18.
[10]WANG Y,SUN T,SUN H,et al.SCF/C-Kit/JNK/AP-1signaling pathway promotes claudin-3 expression in colonic epithelium and colorectal carcinoma[J].Int J Mol Sci,2017,18(4).pii:E765.
[11]KHARMAN-BIZ A,GAO H,GHIASVAND R,et al.Expression of activator protein-1(AP-1)family members in breast cancer[J].BMC Cancer,2013,13(1):441.
[12]BAMBERGER AM,MILDE-LANGOSCH K,ROSSING E,et al.Expression pattern of the AP-1 family in endometrial cancer:correlations with cell cycle regulators[J].J Cancer Res Clin Oncol,2001,127(9):545-550.
[13]OLIVEIRA-FERRER L,ROβLER K,HAUSTEIN V,et al.c-FOS suppresses ovarian cancer progression by changing adhesion[J].Br J Cancer,2014,110(3):753-763.
[14]王晓娟,李娟,傅冰洁,等.慢性髓系白血病患者CD34+CD38-细胞水平Jun B和CDHB基因启动子区域的甲基化状态研究[J].中国实验血液学杂志,2009,17(6):1405-1408.
[15]STABER PB,LINKESCH W,ZAUNER D,et al.Common alterations in gene expression and increased proliferation in recurrent acute myeloid leukemia[J].Oncogene,2004,23(4):894-904.
[16]LAIMER D,DOLZNIG H,KOLLMANN K,et al.PDGFR blockade is a rational and effective therapy for NPMALK-driven lymphomas[J].Nat Med,2012,18(11):1699-1704.
[17]LEVENTAKI V,DRAKOS E,KARANIKOU M,et al.cJUN n-terminal kinase(JNK)is activated and contributes to tumor cell proliferation in classical hodgkin lymphoma[J].Hum Pathol,2014,45(3):565-572.
[18]KIM HJ,EVERS BM,GUO Y,et al.Bombesin-mediated AP-1 activation in a human gastric cancer(SIIA)[J].Surgery,1996,120(2):130-137.
[19]KAWABATA K,MURAKAMI A,OHIGASHI H,et al.Down-Regulates matrix metalloproteinase-7(matrilysin)expression in HT-29 human colorectal cancer cells[J].Biosci Biotechnol Biochem,2005,69(2):307-314.
[20]VALACHOVICOVA T,SLIVOVA V,BERGMAN H,et al.Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappa B/AP-1-dependent and-independent pathways[J].Int J Oncol,2004,25(5):1389-1395.
[21]PAN J,ZHANG Q,XIONG DH,et al.Transcriptomic analysis by RNA-Seq reveals AP-1 pathway as key regulator that green tea May rely on to inhibit lung tumorigenesis[J].Mol Carcinog,2014,53(1):19-29.
[22]WAGNER EF,EFERL R.Fos/AP-1 proteins in bone and the immune system[J].Immunol Rev,2005,208(1):126-140.
[23]MACIAN F,LOPEZ-RODRIGUEZ C,RAO A.Partners in transcription:NFAT and AP-1[J].Oncogene,2001,20(19):2476-2489.
[24]BAZZAZI H,AGHAEI M,MEMARIAN A,et al.Th1-Th17 Ratio as a new insight in rheumatoid arthritis disease[J].Iran J Allergy Asthma Immunol,2018,17(1):68-77.
[25]GONG F,ZHU HY,ZHU J,et al.Circulating CXCR5+CD4+,T cells participate in the Ig E accumulation in allergic asthma[J].Immunol Lett,2018,197:9-14.
[26]NEDOSZYTKO B,SOKOLOWSKA-WOJDYLO M,RENKE J,et al.The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases.Part III:Polymorphisms of genes involved in Tregs’activation and function[J].Postepy Dermatol Alergol,2017,34(6):517-525.
[27]GLIMCHER LH,MURPHY KM.Lineage commitment in the immune system:the T helper lymphocyte grows up[J].Genes Dev,2000,14(14):1693-1711.
[28]TANEL A,FONSECA SG,YASSINE-DIAB B,et al.Cellular and molecular mechanisms of memory T-cell survival[J].Expert Rev Vaccines,2009,8(3):299-312.
[29]WANG ZY,SATO H,KUSAM S,et al.Regulation of IL-10 gene expression in Th2 cells by Jun proteins[J].J Immunol,2005,174(4):2098-3105.
[30]MEIXNER A,KARRETH F,KENNER L,et al.Jun D regulates lymphocyte proliferation and T helper cell cytokine expression[J].EMBO J,2004,23(6):1325-1335.
[31]ROY S,CHARBONEAU R,MELNYK D,et al.Interleukin-4 regulates macrophage interleukin-12 protein synthesis through a c-fos mediated mechanism[J].Surgery,2000,128(2):219-224.
[32]DE BOSSCHER K,BECK IM,RATMAN D,et al.Activation of the glucocorticoid receptor in acute inflammation:the SEDIGRAM concept[J].Trends Pharmacol Sci,2016,37(1):4-16.
[33]WEIKUM ER,DE VERA IMS,NWACHUKWU JC,et al.Tethering not required:the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes[J].Nucleic Acids Res,2017,45(14):8596-8608.
[34]OH KS,PATEL H,GOTTSCHALK RA,et al.Anti-inflammatory chromatinscape suggests alternative mechanisms of glucocorticoid receptor action[J].Immunity,2017,47(2):298-309.
[35]ROY A,SRIVASTAVA M,SAQIB U,et al.Potential therapeutic targets for inflammation in toll-like receptor 4(TLR4)-mediated signaling pathways[J].Int Immunopharmacol,2016,40:79-89.
[36]RATAJCZAK-WRONA W,JABLONSKA E,GARLEY MA,et al.Role of AP-1 family proteins in regulation of inducible nitric oxide synthase(i NOS)in human neutrophils[J].J Immunotoxicol,2013,10(1):32-39.
基本信息:
DOI:10.16424/j.cnki.cn32-1807/r.2018.01.013
中图分类号:R363
引用信息:
[1]伍培,赵建美.AP-1的研究进展[J].南通大学学报(医学版),2018,38(01):41-45.DOI:10.16424/j.cnki.cn32-1807/r.2018.01.013.
基金信息:
江苏省卫生厅科研项目(H201423);; 江苏省卫计委妇幼健康科研项目(F201751);; 南通市科技计划项目(MS22015071)