泛素-蛋白酶体系统在昆虫先天免疫中的调控作用
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摘要
完善的先天免疫系统使得昆虫成为分布最广、适应性最强、物种多样性最丰富的动物类群。在长期的进化过程中,昆虫建立了一套安全有效的先天免疫系统,一方面在面对外界微生物攻击的时候及时有效的发生免疫应答反应;另一方面通过免疫抑制来调控适度免疫应答,避免对自身发动攻击和控制环境共生菌刺激引起的免疫应答信号通路的持续激活。泛素-蛋白酶体系统在昆虫先天免疫中具有重要的调控作用,在Toll和IMD信号通路中,通过对免疫应答通路中信号分子的泛素化修饰加工,促进或抑制抗菌肽的表达,从而使免疫反应达到一个平衡。本文通过对泛素-蛋白酶体系统在Toll和IMD信号通路中的免疫应答和免疫抑制方面的研究进行综述,阐明了该系统在昆虫先天免疫中的调控作用,将有助于开展农业害虫与其天敌之间相互关系的深入研究,揭示其免疫调控机理,为开发生物农药,进行生物防控提供理论依据。
Insects are the most widely distributed,adaptable and biodiverse groups of animals due to its perfection of innate immune system. In the long- term evolutionary process,insects develop a safe and effective innate immune system. On one hand,a timely and effective immune response reaction will start in the face of microbial attack. On the other hand,the appropriate immune response is regulated by immune suppression,avoiding the attack on their own and controlling the continuous response stimulated by resident bacteria. Ubiquitin- Proteasome System( UPS) has played an important role in the regulation of the innate immune in insects. In the Toll and IMD signal pathway,the UPS promotes or inhibits the expression of antimicrobial peptides with the modification and processing in signal molecules to reach a balance in immune response. This review summarizes the recent advances about the function of Ubiquitin- Proteasome System in Toll and IMD signal pathway on immune response and immune suppression,and then sheds light on the regulation of the innate immune in insects conducted by Ubiquitin- Proteasome System,for promoting the research in the relationship between the agricultural pests and its natural enemy, elucidating the mechanism of immune regulation, being helpful in developing biological pesticide and providing theoretical basis for biological control.
Insects are the most widely distributed,adaptable and biodiverse groups of animals due to its perfection of innate immune system. In the long- term evolutionary process,insects develop a safe and effective innate immune system. On one hand,a timely and effective immune response reaction will start in the face of microbial attack. On the other hand,the appropriate immune response is regulated by immune suppression,avoiding the attack on their own and controlling the continuous response stimulated by resident bacteria. Ubiquitin- Proteasome System( UPS) has played an important role in the regulation of the innate immune in insects. In the Toll and IMD signal pathway,the UPS promotes or inhibits the expression of antimicrobial peptides with the modification and processing in signal molecules to reach a balance in immune response. This review summarizes the recent advances about the function of Ubiquitin- Proteasome System in Toll and IMD signal pathway on immune response and immune suppression,and then sheds light on the regulation of the innate immune in insects conducted by Ubiquitin- Proteasome System,for promoting the research in the relationship between the agricultural pests and its natural enemy, elucidating the mechanism of immune regulation, being helpful in developing biological pesticide and providing theoretical basis for biological control.
引文
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Bhaskar V,Valentine SA,Courey AJ.A functional interaction betweendorsal and components of the Smt3 conjugation machinery[J].Journal of Biological Chemistry,2000,275(6):4033-4040.
Bhaskar V,Smith M,Courey AJ.Conjugation of Smt3 to dorsal maypotentiate the Drosophila immune response[J].Mol.Cell.Biol,2002,22(2):492-504.
Buchon N,Poidevin M,Kwon HM,et al.A single modular serineprotease integrates signals from pattern-recognition receptorsupstream of the Drosophila Toll pathway[J].Proc.Natl.Acad.Sci.U.S.A.,2009,106(30):12442-12447.
Chen JH,Tang ZH.The ubiquitin-proteasome system and its role inimmune system[J].International Journal of Immunology,2010,33(4):286-288.[陈建华,汤正好.泛素-蛋白酶体系统与免疫系统的关系[J].国际免疫学杂志,2010,33(4):286-288]
Choe KM,Werner T,Stoven S,et al.Requirement for a peptidoglycanrecognition protein(PGRP)in Relish activation and antibacterialimmune responses in Drosophila[J].Science,2002,296(5566):359-362.
Ciechanover A,Orian A,Schwartz AL.Ubiquitin-mediatedproteolysis:biological regulation via destruction[J].Bioessays,2000,22(5):442-451.
Daigneault J,Klemetsaune L,Wasserman SA.The IRAK homolog Pelleis the functional counterpart of IκB kinase in the Drosophila Tollpathway[J].Plos One,2013,8(9):e75150.
Engel E,Viargues P,Mortier M,et al.Identifying USPs regulatingimmune signals in Drosophila USP2 deubiquitinates Imd andpromotes its degradation by interacting with the proteasome[J].Cell Commun.Signal,2014,12(41).
Feldhaar H,Gross R.Immune reactions of insects on bacterialpathogens and mutualists[J].Microbes Infect,2008,10(9):1082-1088.
Fernando MDA,Kounatidis I,Ligoxygakis P.Loss of trabid,a newnegative regulator of the Drosophila immune-deficiency pathway atthe Level of TAK1,reduces life span[J].Plos Genetics,2014,10(2):e1004117.
Ferrandon D,Imler JL,Hetru C,et al.The Drosophila systemic immuneresponse:sensing and signalling during bacterial and fungalinfections[J].Nat.Rev.Immunol.,2007,7(11):862-874.
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Guntermann S,Primrose DA,Foley E.Dnr1-dependent regulation ofthe Drosophila immune deficiency signaling pathway[J].Dev.Comp.Immunol.,2009,33(1):127-134.
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Hochstrasser M.Origin and function of ubiquitin-like proteins[J].Nature,2009,458(7237):422-429.
Huh JR,Foe I,Muro I,et al.The Drosophila inhibitor of apoptosis(IAP)DIAP2 is dispensable for cell survival,required for theinnate immune response to gram-negative bacterial infection,andcan be negatively regulated by the Reaper/Hid/Grim family of IAP-binding apoptosis inducers[J].Journal of Biological Chemistry,2007,282(3):2056-2068.
Jia YX,Huang B,Zhong H.Strategies of viral attacking celluarubiquitination-proteasome pathway as an anti-innate immunity[J].Letters in Biotechnology,2008,19(5):731-733.[贾永侠,黄蓓,钟辉.病毒攻击泛素蛋白酶体逃逸先天免疫的策略[J].生物技术通讯,2008,19(5):731-733]
Kanayama A,Seth RB,Sun L,et al.TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains[J].Mol.Cell,2004,15(4):535-548.
Karin M,Lin A.NF-kappaB at the crossroads of life and death[J].Nat.Immunol.,2002,3(3):221-7.
Karin M,Greten FR.NF-kappaB:linking inflammation and immunityto cancer development and progression[J].Nat.Rev.Immunol.,2005,5(10):749-59.
Khush RS,Cornwell WD,Uram JN,et al.A ubiquitin-proteasomepathway represses the drosophila immune deficiency signalingcascade[J].Curr.Biol.,2002,15(20):1728-1737.
Kim T,Kim YJ.Overview of innate immunity in Drosophila[J].J.Biochem.Mol.Biol.,2005,38(2):121-127.
Kleino A,Valanne S,Ulvila J,et al.Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway[J].EMBO J.,2005,24(19):3423-3434.
Lemaitre B,Hoffmann J.The host defense of Drosophila melanogaster[J].Annu.Rev.Immunol.,2007,25:697-743.
Leulier F,Vidal S,Saigo K,et al.Inducible expression of doublestranded RNA reveals a role for d FADD in the regulation of theantibacterial response in Drosophila adults[J].Curr.Biol.,2002,12(12):996-1000.
Leulier F,Parquet C,Pili-Floury S,et al.The Drosophila immunesystem detects bacteria through specific peptidoglycan recognition[J].Nature Immunology,2003,4(5):478-484.
Leulier F,Lhocine N,Lemaitre B,et al.The Drosophila inhibitor ofapoptosis protein DIAP2 functions in innate immunity and isessential to resist gram-negative bacterial infection[J].Mol.CellBiol.,2006,26(21):7821-7831.
Leulier F.Tuning down NF-kappaB signaling by DUBs:a fly case[J].Cell Host Microbe,2009,6(4):294-296.
Li M,Pang ZY,Xiao W,et al.A transcriptome analysis suggestsapoptosis-related signaling pathways in hemocytes of Spodopteralitura after parasitization by Microplitis bicoloratus[J].PLoS One,2014,9(10):e110967.
Li Q,Withoff S,Verma IM.Inflammation-associated cancer:NFkappaB is the lynchpin[J].Trends Immunol,2005,26(6):318-25.
Liu T,Luo KJ.Immunity-related domains of Toll and IMD signalingpathways in Drosophila[J].Journal of Environmental Entomology,2011,33(3):388-395.[刘甜,罗开珺.果蝇Toll和IMD信号通路中的功能结构域[J].环境昆虫学报,2011,33(3):388-395]
Lu Y,Wu LP,Anderson KV.The antibacterial arm of the drosophilainnate immune response requires an IkappaB kinase[J].GenesDev.,2001,15(1):104-110.
Malynn BA,Ma A.Ubiquitin makes its mark on immune regulation[J].Immunity,2010,33(6):843-852.
Marmaras VJ,Lampropoulou M.Regulators and signalling in insecthaemocyte immunity[J].Cell Signal,2009,21(2):186-195.
Meinander A,Runchel C,Tenev T,et al.Ubiquitylation of the initiatorcaspase DREDD is required for innate immune signalling[J].EMBO J,2012,31(12):2770-2783.
Naitza S,Rosse C,Kappler C,et al.The Drosophila immune defenseagainst gram-negative infection requires the death protein d FADD[J].Immunity,2002,17(5):575-581.
Nappi AJ,Ottaviani E.Cytotoxicity and cytotoxic molecules ininvertebrates[J].Bioessays,2000,22(5):469-480.
Ni XG,Zhao P.The composition and function of the ubiquitinproteasome pathway[J].Progress in Physiological,2006,37(3):255-258.[倪晓光,赵平.泛素-蛋白酶体途径的组成和功能[J].生理学科学进展,2006,37(3):255-258]
Paquette N,Broemer M,Aggarwal K,et al.Caspase-mediatedcleavage,IAP binding,and ubiquitination:linking threemechanisms crucial for Drosophila NF-kappaB signaling[J].Mol.Cell,2010,37(2):172-182.
Robinson PA,Ardley HC.Ubiquitin-protein ligases[J].Journal ofCell Science,2004,117(Pt22):5191-5194.
Rutschmann S,Jung AC,Zhou R,et al.Role of Drosophila IKK gammain a toll-independent antibacterial immune response[J].NatureImmunology,2000,1(4):342-347.
Shen ZJ,Xu XS,Li T.Ubiquitin-proteasome and its inhibitors[J].Journal of Modern Oncology,2006,14(11):1454-1457.[沈子津,许啸声,李稻.泛素-蛋白酶体及其抑制剂[J].现代肿瘤医学,2006,14(11):1454-1457]
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Silverman N,Zhou R,Erlich RL,et al.Immune activation of NFkappaB and JNK requires Drosophila TAK1[J].J.Biol.Chem.,2003,278(49):48928-48934.
Thevenon D,Engel E,Avet-Rochex A,et al.The Drosophila ubiquitin-specific protease d USP36/Scny targets IMD to prevent constitutiveimmune signaling[J].Cell Host Microbe,2009,6(4):309-320.
Tsichritzis T,Gaentzsch PC,Kosmidis S,et al.A Drosophila ortholog ofthe human cylindromatosis tumor suppressor gene regulatestriglyceride content and antibacterial defense[J].Development,2007,134(14):2605-2614.
Tsuda M,Langmann C,Harden N,et al.The RING-finger scaffoldprotein Plenty of SH3s targets TAK1 to control immunity signallingin Drosophila[J].EMBO Rep.,2005,6(11):1082-1087.
Vidal S,Khush RS,Leulier F,et al.Mutations in the Drosophilad TAK1 gene reveal a conserved function for MAPKKKs in thecontrol of rel/NF-kappaB-dependent innate immune responses[J].Genes Dev.,2001,15(15):1900-1912.
Wang C,Deng L,Hong M,et al.TAK1 is a ubiquitin-dependentkinase of MKK and IKK[J].Nature,2001,412(6844):346-351.
Wang SX,Liu Y,Wu HJ,et al.Advance in research on thedeubiquitinating enzyme[J].Chinese Jouranl of Clinical andExperimental Pathology,2008,24(6):734-737.[王素霞,刘媛,吴慧娟,等.去泛素化酶的研究及其进展[J].临床与实验病理学杂志,2008,24(6):734-737]
Weber AN,Gangloff M,Moncrieffe MC,et al.Role of the Spatzle Prodomain in the generation of an active toll receptor ligand[J].J.Biol.Chem.,2007,282(18):13522-13531.
Williams MJ.Drosophila hemopoiesis and cellular immunity[J].J.Immunol.,2007,178(8):4711-4716.
Xu HP,Hao W,He D,et al.Smt3 is required for the immune responseof silkworm,Bombyx mori[J].Biochimie,2010,92(10):1306-1314.
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Zhuang ZH,Sun L,Kong L,et al.Drosophila TAB2 is required for theimmune activation of JNK and NF-kappaB[J].Cell Signal,2007,19(11):2413-2413.
Aparicio R,Neyen C,Lemaitre B,et al.dRYBP contributes to thenegative regulation of the Drosophila Imd pathway[J].PLoS One,2013,8(4):e62052.
Bhaskar V,Valentine SA,Courey AJ.A functional interaction betweendorsal and components of the Smt3 conjugation machinery[J].Journal of Biological Chemistry,2000,275(6):4033-4040.
Bhaskar V,Smith M,Courey AJ.Conjugation of Smt3 to dorsal maypotentiate the Drosophila immune response[J].Mol.Cell.Biol,2002,22(2):492-504.
Buchon N,Poidevin M,Kwon HM,et al.A single modular serineprotease integrates signals from pattern-recognition receptorsupstream of the Drosophila Toll pathway[J].Proc.Natl.Acad.Sci.U.S.A.,2009,106(30):12442-12447.
Chen JH,Tang ZH.The ubiquitin-proteasome system and its role inimmune system[J].International Journal of Immunology,2010,33(4):286-288.[陈建华,汤正好.泛素-蛋白酶体系统与免疫系统的关系[J].国际免疫学杂志,2010,33(4):286-288]
Choe KM,Werner T,Stoven S,et al.Requirement for a peptidoglycanrecognition protein(PGRP)in Relish activation and antibacterialimmune responses in Drosophila[J].Science,2002,296(5566):359-362.
Ciechanover A,Orian A,Schwartz AL.Ubiquitin-mediatedproteolysis:biological regulation via destruction[J].Bioessays,2000,22(5):442-451.
Daigneault J,Klemetsaune L,Wasserman SA.The IRAK homolog Pelleis the functional counterpart of IκB kinase in the Drosophila Tollpathway[J].Plos One,2013,8(9):e75150.
Engel E,Viargues P,Mortier M,et al.Identifying USPs regulatingimmune signals in Drosophila USP2 deubiquitinates Imd andpromotes its degradation by interacting with the proteasome[J].Cell Commun.Signal,2014,12(41).
Feldhaar H,Gross R.Immune reactions of insects on bacterialpathogens and mutualists[J].Microbes Infect,2008,10(9):1082-1088.
Fernando MDA,Kounatidis I,Ligoxygakis P.Loss of trabid,a newnegative regulator of the Drosophila immune-deficiency pathway atthe Level of TAK1,reduces life span[J].Plos Genetics,2014,10(2):e1004117.
Ferrandon D,Imler JL,Hetru C,et al.The Drosophila systemic immuneresponse:sensing and signalling during bacterial and fungalinfections[J].Nat.Rev.Immunol.,2007,7(11):862-874.
Gesellchen V,Kuttenkeuler D,Steckel M,et al.An RNA interferencescreen identifies Inhibitor of Apoptosis Protein 2 as a regulator ofinnate immune signalling in Drosophila[J].EMBO Rep.,2005,6(10):979-984.
Gottar M,Gobert V,Michel T,et al.The Drosophila immune responseagainst Gram-negative bacteria is mediated by a peptidoglycanrecognition protein[J].Nature,2002,416(6881):640-644.
Guntermann S,Primrose DA,Foley E.Dnr1-dependent regulation ofthe Drosophila immune deficiency signaling pathway[J].Dev.Comp.Immunol.,2009,33(1):127-134.
He L,Wang QQ.Advance in research on the regulation of innateimmune response by ubiquitination[J].International Journal ofImmunology,2014,37(2):91-96.[何丽,王青青.泛素化对固有免疫应答的调控研究进展[J].国际免疫学杂志,2014,37(2):91-96]
Hochstrasser M.Origin and function of ubiquitin-like proteins[J].Nature,2009,458(7237):422-429.
Huh JR,Foe I,Muro I,et al.The Drosophila inhibitor of apoptosis(IAP)DIAP2 is dispensable for cell survival,required for theinnate immune response to gram-negative bacterial infection,andcan be negatively regulated by the Reaper/Hid/Grim family of IAP-binding apoptosis inducers[J].Journal of Biological Chemistry,2007,282(3):2056-2068.
Jia YX,Huang B,Zhong H.Strategies of viral attacking celluarubiquitination-proteasome pathway as an anti-innate immunity[J].Letters in Biotechnology,2008,19(5):731-733.[贾永侠,黄蓓,钟辉.病毒攻击泛素蛋白酶体逃逸先天免疫的策略[J].生物技术通讯,2008,19(5):731-733]
Kanayama A,Seth RB,Sun L,et al.TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains[J].Mol.Cell,2004,15(4):535-548.
Karin M,Lin A.NF-kappaB at the crossroads of life and death[J].Nat.Immunol.,2002,3(3):221-7.
Karin M,Greten FR.NF-kappaB:linking inflammation and immunityto cancer development and progression[J].Nat.Rev.Immunol.,2005,5(10):749-59.
Khush RS,Cornwell WD,Uram JN,et al.A ubiquitin-proteasomepathway represses the drosophila immune deficiency signalingcascade[J].Curr.Biol.,2002,15(20):1728-1737.
Kim T,Kim YJ.Overview of innate immunity in Drosophila[J].J.Biochem.Mol.Biol.,2005,38(2):121-127.
Kleino A,Valanne S,Ulvila J,et al.Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway[J].EMBO J.,2005,24(19):3423-3434.
Lemaitre B,Hoffmann J.The host defense of Drosophila melanogaster[J].Annu.Rev.Immunol.,2007,25:697-743.
Leulier F,Vidal S,Saigo K,et al.Inducible expression of doublestranded RNA reveals a role for d FADD in the regulation of theantibacterial response in Drosophila adults[J].Curr.Biol.,2002,12(12):996-1000.
Leulier F,Parquet C,Pili-Floury S,et al.The Drosophila immunesystem detects bacteria through specific peptidoglycan recognition[J].Nature Immunology,2003,4(5):478-484.
Leulier F,Lhocine N,Lemaitre B,et al.The Drosophila inhibitor ofapoptosis protein DIAP2 functions in innate immunity and isessential to resist gram-negative bacterial infection[J].Mol.CellBiol.,2006,26(21):7821-7831.
Leulier F.Tuning down NF-kappaB signaling by DUBs:a fly case[J].Cell Host Microbe,2009,6(4):294-296.
Li M,Pang ZY,Xiao W,et al.A transcriptome analysis suggestsapoptosis-related signaling pathways in hemocytes of Spodopteralitura after parasitization by Microplitis bicoloratus[J].PLoS One,2014,9(10):e110967.
Li Q,Withoff S,Verma IM.Inflammation-associated cancer:NFkappaB is the lynchpin[J].Trends Immunol,2005,26(6):318-25.
Liu T,Luo KJ.Immunity-related domains of Toll and IMD signalingpathways in Drosophila[J].Journal of Environmental Entomology,2011,33(3):388-395.[刘甜,罗开珺.果蝇Toll和IMD信号通路中的功能结构域[J].环境昆虫学报,2011,33(3):388-395]
Lu Y,Wu LP,Anderson KV.The antibacterial arm of the drosophilainnate immune response requires an IkappaB kinase[J].GenesDev.,2001,15(1):104-110.
Malynn BA,Ma A.Ubiquitin makes its mark on immune regulation[J].Immunity,2010,33(6):843-852.
Marmaras VJ,Lampropoulou M.Regulators and signalling in insecthaemocyte immunity[J].Cell Signal,2009,21(2):186-195.
Meinander A,Runchel C,Tenev T,et al.Ubiquitylation of the initiatorcaspase DREDD is required for innate immune signalling[J].EMBO J,2012,31(12):2770-2783.
Naitza S,Rosse C,Kappler C,et al.The Drosophila immune defenseagainst gram-negative infection requires the death protein d FADD[J].Immunity,2002,17(5):575-581.
Nappi AJ,Ottaviani E.Cytotoxicity and cytotoxic molecules ininvertebrates[J].Bioessays,2000,22(5):469-480.
Ni XG,Zhao P.The composition and function of the ubiquitinproteasome pathway[J].Progress in Physiological,2006,37(3):255-258.[倪晓光,赵平.泛素-蛋白酶体途径的组成和功能[J].生理学科学进展,2006,37(3):255-258]
Paquette N,Broemer M,Aggarwal K,et al.Caspase-mediatedcleavage,IAP binding,and ubiquitination:linking threemechanisms crucial for Drosophila NF-kappaB signaling[J].Mol.Cell,2010,37(2):172-182.
Robinson PA,Ardley HC.Ubiquitin-protein ligases[J].Journal ofCell Science,2004,117(Pt22):5191-5194.
Rutschmann S,Jung AC,Zhou R,et al.Role of Drosophila IKK gammain a toll-independent antibacterial immune response[J].NatureImmunology,2000,1(4):342-347.
Shen ZJ,Xu XS,Li T.Ubiquitin-proteasome and its inhibitors[J].Journal of Modern Oncology,2006,14(11):1454-1457.[沈子津,许啸声,李稻.泛素-蛋白酶体及其抑制剂[J].现代肿瘤医学,2006,14(11):1454-1457]
Silverman N,Zhou R,Stoven S,et al.A Drosophila IkappaB kinasecomplex required for Relish cleavage and antibacterial immunity[J].Genes Dev.,2000,14(19):2461-2471.
Silverman N,Zhou R,Erlich RL,et al.Immune activation of NFkappaB and JNK requires Drosophila TAK1[J].J.Biol.Chem.,2003,278(49):48928-48934.
Thevenon D,Engel E,Avet-Rochex A,et al.The Drosophila ubiquitin-specific protease d USP36/Scny targets IMD to prevent constitutiveimmune signaling[J].Cell Host Microbe,2009,6(4):309-320.
Tsichritzis T,Gaentzsch PC,Kosmidis S,et al.A Drosophila ortholog ofthe human cylindromatosis tumor suppressor gene regulatestriglyceride content and antibacterial defense[J].Development,2007,134(14):2605-2614.
Tsuda M,Langmann C,Harden N,et al.The RING-finger scaffoldprotein Plenty of SH3s targets TAK1 to control immunity signallingin Drosophila[J].EMBO Rep.,2005,6(11):1082-1087.
Vidal S,Khush RS,Leulier F,et al.Mutations in the Drosophilad TAK1 gene reveal a conserved function for MAPKKKs in thecontrol of rel/NF-kappaB-dependent innate immune responses[J].Genes Dev.,2001,15(15):1900-1912.
Wang C,Deng L,Hong M,et al.TAK1 is a ubiquitin-dependentkinase of MKK and IKK[J].Nature,2001,412(6844):346-351.
Wang SX,Liu Y,Wu HJ,et al.Advance in research on thedeubiquitinating enzyme[J].Chinese Jouranl of Clinical andExperimental Pathology,2008,24(6):734-737.[王素霞,刘媛,吴慧娟,等.去泛素化酶的研究及其进展[J].临床与实验病理学杂志,2008,24(6):734-737]
Weber AN,Gangloff M,Moncrieffe MC,et al.Role of the Spatzle Prodomain in the generation of an active toll receptor ligand[J].J.Biol.Chem.,2007,282(18):13522-13531.
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