Deneddylation修饰酶NEDP1的作用机制及研究进展
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摘要
神经前体表达发育下调蛋白8(neural precursor cell-expressed developmentally downregulated 8,Nedd8)是一种类泛素蛋白,其参与蛋白质修饰的作用机制与泛素高度相似,即通过与底物的赖氨酸残基共价结合,从而对底物进行Neddylation修饰。Neddylation修饰可调控多种重要的生命活动,如细胞周期和免疫应答等。Nedd8蛋白酶1(Nedd8 protease 1, NEDP1)是隶属于小类泛素修饰物特异性蛋白酶家族(small ubiquitin-like modifier specific protease family, Ulp/Senp family)家族的半胱氨酸蛋白酶,可以特异性去除底物与Nedd8的共价结合,例如,NEDP1能够去除p53、鼠双微体蛋白(murine double min-utes 2 protein, Mdm2)、smad泛素化调节因子1(smad ubiquitylation regulatory factor 1, Smurf1)等多个蛋白质的Neddylation修饰,进而调节Neddylation修饰蛋白的生物学功能。临床研究表明,NEDP1与肿瘤的发生发展密切相关,包括肺癌、结肠癌、胶质母细胞瘤等,另外,NEDP1还参与成骨发育异常、神经退行性疾病、血管炎症等病变过程。本文对NEDP1蛋白的结构,调控Neddylation通路的作用模式和NEDP1作用底物的进展进行总结,以期为肿瘤等相关疾病的诊断和治疗提供参考。
Neural precursor cell-expressed developmentally downregulated 8(Nedd8), a ubiquitin-like protein, whose mechanism of action involved in protein modification, is highly similar to ubiquitin, that is,by covalently binding to the lysine residue of the substrate, the substrate is subjected to Neddylation modification. Neddylation modification can regulate a variety of important life activities, such as cell cycle and immune response. Nedd8 protease 1(NEDP8) is a cysteine protease belonging to small ubiquitin-like modifier specific protease family that specifically removes the covalent attachment of substrates to Nedd8, for example,NEDP1 is able to remove Neddylation modifications of multiple proteins such as p53, murine double minutes2 protein(Mdm2) and smad ubiquitylation regulatory factor 1(Smurf1) to regulate the biological function of Neddylation-modified proteins. Clinical studies have shown that NEDP1 is closely related to the occurrence and development of tumors, including lung cancer, colon cancer, glioblastoma, etc. In addition, NEDP1 is also involved in osteogenic dysplasia, neurodegenerative disease, vascular inflammation and other pathological processes. In this paper, we summarize the structure of NEDP1 protein, the mode of action of regulating the Neddylation pathway and the progress of NEDP1 substrate, in order to provide reference for the diagnosis and treatment of tumor and other related diseases.
Neural precursor cell-expressed developmentally downregulated 8(Nedd8), a ubiquitin-like protein, whose mechanism of action involved in protein modification, is highly similar to ubiquitin, that is,by covalently binding to the lysine residue of the substrate, the substrate is subjected to Neddylation modification. Neddylation modification can regulate a variety of important life activities, such as cell cycle and immune response. Nedd8 protease 1(NEDP8) is a cysteine protease belonging to small ubiquitin-like modifier specific protease family that specifically removes the covalent attachment of substrates to Nedd8, for example,NEDP1 is able to remove Neddylation modifications of multiple proteins such as p53, murine double minutes2 protein(Mdm2) and smad ubiquitylation regulatory factor 1(Smurf1) to regulate the biological function of Neddylation-modified proteins. Clinical studies have shown that NEDP1 is closely related to the occurrence and development of tumors, including lung cancer, colon cancer, glioblastoma, etc. In addition, NEDP1 is also involved in osteogenic dysplasia, neurodegenerative disease, vascular inflammation and other pathological processes. In this paper, we summarize the structure of NEDP1 protein, the mode of action of regulating the Neddylation pathway and the progress of NEDP1 substrate, in order to provide reference for the diagnosis and treatment of tumor and other related diseases.
引文
[1]Varshavsky A.The ubiquitin system.Trends Biochem Sci,1997,22(10):383-387
[2]Kerscher O,Felberbaum R,Hochstrasser M.Modification of proteins by ubiquitin and ubiquitin-like proteins.Annu Rev Cell Dev Biol,2006,22:159-180
[3]Chairatvit K,Ngamkitidechakul C.Control of cell proliferation via elevated NEDD8 conjugation in oral squamous cell carcinoma.Mol Cell Biochem,2007,306(1-2):163-169
[4]Salon C,Brambilla E,Brambilla C,et al.Altered pattern of Cul-1 protein expression and neddylation in human lung tumours:relationships with CAND1 and cyclin Eprotein levels.J Pathol,2007,213(3):303-310
[5]Mori F,Nishie M,Piao YS,et al.Accumulation of NEDD8 in neuronal and glial inclusions of neurodegenerative disorders.Neuropathol Appl Neurobiol,2005,31(1):53-61
[6]Dil K A,Kito K,Abe Y,et al.NEDD8 protein is involved in ubiquitinated inclusion bodies.J Pathol,2003,199(2):259-266
[7]Kumar S,Tomooka Y,Noda M.Identification of a set of genes with developmentally down-regulated expression in the mouse brain.Biochem Biophys Res Commun,1992,185(3):1155-1161
[8]Kamitani T,Kito K,Fukuda-Kamitani T,et al.Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1.J Biol Chem,2001,276(49):46655-46660
[9]Pozo JC,Timpte C,Tan S,et al.The ubiquitin-related protein RUB1 and auxin response in arabidopsis.Science,1998,280(5370):1760-1763
[10]Wu K,Yamoah K,Dolios G,et al.DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1.JBiol Chem,2003,278(31):28882-28891
[11]Mendoza HM,Shen LN,Botting C,et al.NEDP1,a highly conserved cysteine protease that deNEDDylates Cullins.J Biol Chem,2003,278(28):25637-25643
[12]Morimoto M,Nishida T,Nagayama Y,et al.Nedd8-modification of Cul1 is promoted by Roc1 as a Nedd8-E3ligase and regulates its stability.Biochem Biophys Res Commun,2003,301(2):392-398
[13]Kurz T,Chou YC,Willems AR,et al.Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation.Mol Cell,2008,29(1):23-35
[14]Xirodimas DP,Saville MK,Bourdon JC,et al.Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity.Cell,2004,118(1):83-97
[15]Yang X,Zhou J,Sun L,et al.Structural basis for the function of DCN-1 in protein Neddylation.J Biol Chem,2007,282(34):24490-24494
[16]Broemer M,Tenev T,Rigbolt KT,et al.Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases.Mol Cell,2010,40(5):810-822
[17]Li T,Guan J,Huang Z,et al.RNF168-mediated H2Aneddylation antagonizes ubiquitylation of H2A and regulates DNA damage repair.J Cell Sci,2014,127(Pt 10):2238-2248
[18]Ma T,Chen Y,Zhang F,et al.RNF111-dependent neddylation activates DNA damage-induced ubiquitination.Mol Cell,2013,49(5):897-907
[19]Xie P,Zhang M,He S,et al.The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis.Nat Commun,2014,5:3733
[20]Shu J,Liu C,Wei R,et al.Nedd8 targets ubiquitin ligase Smurf2 for neddylation and promote its degradation.Biochem Biophys Res Commun,2016,474(1):51-56
[21]Li H,Zhu H,Liu Y,et al.Itch promotes the neddylation of JunB and regulates JunB-dependent transcription.Cell Signal,2016,28(9):1186-1195
[22]Huang DT,Walden H,Duda D,et al.Ubiquitin-like protein activation.Oncogene,2004,23(11):1958-1971
[23]Hori T,Osaka F,Chiba T,et al.Covalent modification of all members of human cullin family proteins by NEDD8.Oncogene,1999,18(48):6829-6834
[24]Jones J,Wu K,Yang Y,et al.A targeted proteomic analysis of the ubiquitin-like modifier nedd8 and associated proteins.J Proteome Res,2008,7(3):1274-1287
[25]Stickle NH,Chung J,Klco JM,et al.pVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development.Mol Cell Biol,2004,24(8):3251-3261
[26]Najor NA,Fitz GN,Koetsier JL,et al.Epidermal growth factor receptor neddylation is regulated by a desmosomal-COP9(Constitutive Photomorphogenesis 9)signalosome complex.Elife,2017,6:e22599
[27]Gao F,Cheng J,Shi T,et al.Neddylation of a breast cancer-associated protein recruits a class III histone deacetylase that represses NFkappaB-dependent transcription.Nat Cell Biol,2006,8(10):1171-1177
[28]Xirodimas DP,Sundqvist A,Nakamura A,et al.Ribosomal proteins are targets for the NEDD8 pathway.EMBO Rep,2008,9(3):280-286
[29]Loftus SJ,Liu G,Carr SM,et al.Neddylation regulates E2F-1-dependent transcription.EMBO Rep,2012,13(9):811-818
[30]Park HS,Ju UI,Park JW,et al.PPARgamma neddylation essential for adipogenesis is a potential target for treating obesity.Cell Death Differ,2016,23(8):1296-1311
[31]Jayabalan AK,Sanchez A,Park RY,et al.NEDDylation promotes stress granule assembly.Nat Commun,2016,7:12125
[32]Kuriu T,Inoue A,Bito H,et al.Differential control of postsynaptic density scaffolds via actin-dependent and-independent mechanisms.J Neurosci,2006,26(29):7693-7706
[33]Vallejo D,Codocedo JF,Inestrosa NC.Posttranslational modifications regulate the postsynaptic localization of PSD-95.Mol Neurobiol,2017,54(3):1759-1776
[34]Zhang T,Ye Z,Yang X,et al.Neddylation of PB2 reduces its stability and blocks the replication of influenza a virus.Sci Rep,2017,7:43691
[35]Petroski MD,Deshaies RJ.Function and regulation of cullin-RING ubiquitin ligases.Nat Rev Mol Cell Biol,2005,6(1):9-20
[36]Lipkowitz S,Weissman AM.RINGs of good and evil:RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis.Nat Rev Cancer,2011,11(9):629-643
[37]Watson IR,Li BK,Roche O,et al.Chemotherapy induces NEDP1-mediated destabilization of MDM2.Oncogene,2010,29(2):297-304
[38]Abida WM,Nikolaev A,Zhao W,et al.FBXO11 promotes the Neddylation of p53 and inhibits its transcriptional activity.J Biol Chem,2007,282(3):1797-1804
[39]Russell RC,Ohh M.NEDD8 acts as a'molecular switch defining the functional selectivity of VHL.EMBO Rep,2008,9(5):486-491
[40]Watson IR,Blanch A,Lin DC,et al.Mdm2-mediated NEDD8 modification of TAp73 regulates its transactivation function.J Biol Chem,2006,281(45):34096-34103
[41]Oved S,Mosesson Y,Zwang Y,et al.Conjugation to Nedd8 instigates ubiquitylation and down-regulation of activated receptor tyrosine kinases.J Biol Chem,2006,281(31):21640-21651
[42]Lee MR,Lee D,Shin SK,et al.Inhibition of APP intracellular domain(AICD)transcriptional activity via covalent conjugation with Nedd8.Biochem Biophys Res Commun,2008,366(4):976-981
[43]Nagano T,Hashimoto T,Nakashima A,et al.X-linked inhibitor of apoptosis protein mediates neddylation by itself but does not function as a NEDD8-E3 ligase for caspase-7.FEBS Lett,2012,586(11):1612-1616
[44]Ryu JH,Li SH,Park HS,et al.Hypoxia-inducible factor alpha subunit stabilization by NEDD8 conjugation is reactive oxygen species-dependent.J Biol Chem,2011,286(9):6963-6970
[45]Mahata B,Sundqvist A,Xirodimas DP.Recruitment of RPL11 at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and in an Mdm2-dependent manner.Oncogene,2012,31(25):3060-3071
[46]Choo YS,Vogler G,Wang D,et al.Regulation of parkin and PINK1 by neddylation.Hum Mol Genet,2012,21(11):2514-2523
[47]Chen Y,Neve RL,Liu H.Neddylation dysfunction in Alzheimer's disease.J Cell Mol Med,2012,16(11):2583-2591
[48]Leidecker O,Matic I,Mahata B,et al.The ubiquitin E1enzyme Ube1 mediates NEDD8 activation under diverse stress conditions.Cell Cycle,2012,11(6):1142-1150
[49]Singh RK,Zerath S,Kleifeld O,et al.Recognition and cleavage of related to ubiquitin 1(Rub1)and Rub1-ubiquitin chains by components of the ubiquitin-proteasome system.Mol Cell Proteomics,2012,11(12):1595-1611
[50]Embade N,Fernandez-Ramos D,Varela-Rey M,et al.Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through Neddylation.Hepatology,2012,55(4):1237-1248
[51]Noh EH,Hwang HS,Hwang HS,et al.Covalent NEDD8conjugation increases RCAN1 protein stability and potentiates its inhibitory action on calcineurin.PLoS One,2012,7(10):e48315
[52]Zhang J,Bai D,Ma X,et al.hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling Neddylation of ribosomal protein S14.Oncogene,2014,33(2):246-254
[53]Jin HS,Liao L,Park Y,et al.Neddylation pathway regulates T-cell function by targeting an adaptor protein Shc and a protein kinase Erk signaling.Proc Natl Acad Sci USA,2013,110(2):624-629
[54]Zuo W,Huang F,Chiang YJ,et al.c-Cbl-mediated neddylation antagonizes ubiquitination and degradation of the TGF-beta type II receptor.Mol Cell,2013,49(3):499-510
[55]Takashima O,Tsuruta F,Kigoshi Y,et al.Brap2 regulates temporal control of NF-kappaB localization mediated by inflammatory response.PLoS One,2013,8(3):e58911
[56]Brown JS,Lukashchuk N,Sczaniecka-Clift M,et al.Neddylation promotes ubiquitylation and release of Ku from DNA-damage sites.Cell Rep,2015,11(5):704-714
[57]Yan F,Guan J,Peng Y,et al.MyD88 Neddylation negatively regulates MyD88-dependent NF-kappaB signaling through antagonizing its ubiquitination.Biochem Biophys Res Commun,2017,482(4):632-637
[58]Coleman KE,Bekes M,Chapman JR,et al.SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin-RING ubiquitin ligase function.Elife,2017,6:e24325
[59]Lyapina S,Cope G,Shevchenko A,et al.Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.Science,2001,292(5520):1382-1385
[60]Cope GA,Suh GS,Aravind L,et al.Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8from Cul1.Science,2002,298(5593):608-611
[61]Seeger M,Gordon C,Dubiel W.Protein stability:the COP9 signalosome gets in on the act.Curr Biol,2001,11(16):R643-R646
[62]Lingaraju GM,Bunker RD,Cavadini S,et al.Crystal structure of the human COP9 signalosome.Nature,2014,512(7513):161-165
[63]Cavadini S,Fischer ES,Bunker RD,et al.Cullin-RINGubiquitin E3 ligase regulation by the COP9 signalosome.Nature,2016,531(7596):598-603
[64]Kim K,Yoon J,Yim J,et al.Deneddylase 1 regulates deneddylase activity of the Cop9 signalosome in Drosophila melanogaster.Insect Sci,2017,24(1):27-34
[65]Chan Y,Yoon J,Wu J T,et al.DEN1 deneddylates non-cullin proteins in vivo.J Cell Sci,2008,121(Pt 19):3218-3223
[66]Shen LN,Liu H,Dong C,et al.Structural basis of NEDD8 ubiquitin discrimination by the deNeddylating enzyme NEDP1.EMBO J,2005,24(7):1341-1351
[67]Whitby FG,Xia G,Pickart CM,et al.Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes.J Biol Chem,1998,273(52):34983-34991
[68]Mergner J,Heinzlmeir S,Kuster B,et al.Deneddylase1deconjugates NEDD8 from non-cullin protein substrates in Arabidopsis thaliana.Plant Cell,2015,27(3):741-753
[69]Bode AM,Dong Z.Post-translational modification of p53 in tumorigenesis.Nat Rev Cancer,2004,4(10):793-805
[70]Qin H,Wang J,Liang Y,et al.RING1 inhibits transactivation of RBP-J by Notch through interaction with LIMprotein KyoT2.Nucleic Acids Res,2004,32(4):1492-1501
[71]Semenza GL.HIF-1 and mechanisms of hypoxia sensing.Curr Opin Cell Biol,2001,13(2):167-171
[72]Semenza GL.Life with oxygen.Science,2007,318(5847):62-64
[73]Nam SY,Ko YS,Jung J,et al.A hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear factor-kappaB promotes gastric tumour growth and angiogenesis.Br J Cancer,2011,104(1):166-174
[74]Baker RG,Hayden MS,Ghosh S.NF-kappaB,inflammation,and metabolic disease.Cell Metab,2011,13(1):11-22
[75]Hayden MS,Ghosh S.Shared principles in NF-kappaBsignaling.Cell,2008,132(3):344-362
[76]Barnes PJ,Karin M.Nuclear factor-kappaB:a pivotal transcription factor in chronic inflammatory diseases.NEngl J Med,1997,336(15):1066-1071
[77]Li Q,Withoff S,Verma IM.Inflammation-associated cancer:NF-kappaB is the lynchpin.Trends Immunol,2005,26(6):318-325
[78]Walmsley SR,Print C,Farahi N,et al.Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity.J Exp Med,2005,201(1):105-115
[79]Belaiba RS,Bonello S,Zahringer C,et al.Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery smooth muscle cells.Mol Biol Cell,2007,18(12):4691-4697
[80]Guan J,Yu S,Zheng X.Neddylation antagonizes ubiquitination of proliferating cell nuclear antigen and regulates the recruitment of polymerase eta in response to oxidative DNA damage.Protein Cell,2018,9(4):365-379
[81]Paunu N,Lahermo P,Onkamo P,et al.A novel low-penetrance locus for familial glioma at 15q23-q26.3.Cancer Res,2002,62(13):3798-3802
[82]Koschny R,Holland H,Koschny T,et al.Comparative genomic hybridization pattern of non-anaplastic and anaplastic oligodendrogliomas--a meta-analysis.Pathol Res Pract,2006,202(1):23-30
[83]Huang HY,West RB,Tzeng CC,et al.Immunohistochemical and biogenetic features of diffuse-type tenosynovial giant cell tumors:the potential roles of cyclin A,P53,and deletion of 15q in sarcomatous transformation.Clin Cancer Res,2008,14(19):6023-6032
[84]Suzuki H,Ouchida M,Yamamoto H,et al.Decreased expression of the SIN3A gene,a candidate tumor suppressor located at the prevalent allelic loss region15q23 in non-small cell lung cancer.Lung Cancer,2008,59(1):24-31
[85]Soucy TA,Smith PG,Milhollen MA,et al.An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer.Nature,2009,458(7239):732-736
[86]Brownell JE,Sintchak MD,Gavin JM,et al.Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes:the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.Mol Cell,2010,37(1):102-111
[87]Luo Z,Yu G,Lee HW,et al.The Nedd8-activating enzyme inhibitor MLN4924 induces autophagy and apoptosis to suppress liver cancer cell growth.Cancer Res,2012,72(13):3360-3371
[88]Soucy TA,Smith PG,Rolfe M.Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer.Clin Cancer Res,2009,15(12):3912-3916
[89]Zhou L,Zhang W,Sun Y,et al.Protein neddylation and its alterations in human cancers for targeted therapy.Cell Signal,2018,44:92-102
[90]Vanderdys V,Allak A,Guessous F,et al.The neddylation inhibitor pevonedistat(MLN4924)suppresses and radiosensitizes head and neck squamous carcinoma cells and tumors.Mol Cancer Ther,2018,17(2):368-380
[2]Kerscher O,Felberbaum R,Hochstrasser M.Modification of proteins by ubiquitin and ubiquitin-like proteins.Annu Rev Cell Dev Biol,2006,22:159-180
[3]Chairatvit K,Ngamkitidechakul C.Control of cell proliferation via elevated NEDD8 conjugation in oral squamous cell carcinoma.Mol Cell Biochem,2007,306(1-2):163-169
[4]Salon C,Brambilla E,Brambilla C,et al.Altered pattern of Cul-1 protein expression and neddylation in human lung tumours:relationships with CAND1 and cyclin Eprotein levels.J Pathol,2007,213(3):303-310
[5]Mori F,Nishie M,Piao YS,et al.Accumulation of NEDD8 in neuronal and glial inclusions of neurodegenerative disorders.Neuropathol Appl Neurobiol,2005,31(1):53-61
[6]Dil K A,Kito K,Abe Y,et al.NEDD8 protein is involved in ubiquitinated inclusion bodies.J Pathol,2003,199(2):259-266
[7]Kumar S,Tomooka Y,Noda M.Identification of a set of genes with developmentally down-regulated expression in the mouse brain.Biochem Biophys Res Commun,1992,185(3):1155-1161
[8]Kamitani T,Kito K,Fukuda-Kamitani T,et al.Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1.J Biol Chem,2001,276(49):46655-46660
[9]Pozo JC,Timpte C,Tan S,et al.The ubiquitin-related protein RUB1 and auxin response in arabidopsis.Science,1998,280(5370):1760-1763
[10]Wu K,Yamoah K,Dolios G,et al.DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1.JBiol Chem,2003,278(31):28882-28891
[11]Mendoza HM,Shen LN,Botting C,et al.NEDP1,a highly conserved cysteine protease that deNEDDylates Cullins.J Biol Chem,2003,278(28):25637-25643
[12]Morimoto M,Nishida T,Nagayama Y,et al.Nedd8-modification of Cul1 is promoted by Roc1 as a Nedd8-E3ligase and regulates its stability.Biochem Biophys Res Commun,2003,301(2):392-398
[13]Kurz T,Chou YC,Willems AR,et al.Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation.Mol Cell,2008,29(1):23-35
[14]Xirodimas DP,Saville MK,Bourdon JC,et al.Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity.Cell,2004,118(1):83-97
[15]Yang X,Zhou J,Sun L,et al.Structural basis for the function of DCN-1 in protein Neddylation.J Biol Chem,2007,282(34):24490-24494
[16]Broemer M,Tenev T,Rigbolt KT,et al.Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases.Mol Cell,2010,40(5):810-822
[17]Li T,Guan J,Huang Z,et al.RNF168-mediated H2Aneddylation antagonizes ubiquitylation of H2A and regulates DNA damage repair.J Cell Sci,2014,127(Pt 10):2238-2248
[18]Ma T,Chen Y,Zhang F,et al.RNF111-dependent neddylation activates DNA damage-induced ubiquitination.Mol Cell,2013,49(5):897-907
[19]Xie P,Zhang M,He S,et al.The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis.Nat Commun,2014,5:3733
[20]Shu J,Liu C,Wei R,et al.Nedd8 targets ubiquitin ligase Smurf2 for neddylation and promote its degradation.Biochem Biophys Res Commun,2016,474(1):51-56
[21]Li H,Zhu H,Liu Y,et al.Itch promotes the neddylation of JunB and regulates JunB-dependent transcription.Cell Signal,2016,28(9):1186-1195
[22]Huang DT,Walden H,Duda D,et al.Ubiquitin-like protein activation.Oncogene,2004,23(11):1958-1971
[23]Hori T,Osaka F,Chiba T,et al.Covalent modification of all members of human cullin family proteins by NEDD8.Oncogene,1999,18(48):6829-6834
[24]Jones J,Wu K,Yang Y,et al.A targeted proteomic analysis of the ubiquitin-like modifier nedd8 and associated proteins.J Proteome Res,2008,7(3):1274-1287
[25]Stickle NH,Chung J,Klco JM,et al.pVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development.Mol Cell Biol,2004,24(8):3251-3261
[26]Najor NA,Fitz GN,Koetsier JL,et al.Epidermal growth factor receptor neddylation is regulated by a desmosomal-COP9(Constitutive Photomorphogenesis 9)signalosome complex.Elife,2017,6:e22599
[27]Gao F,Cheng J,Shi T,et al.Neddylation of a breast cancer-associated protein recruits a class III histone deacetylase that represses NFkappaB-dependent transcription.Nat Cell Biol,2006,8(10):1171-1177
[28]Xirodimas DP,Sundqvist A,Nakamura A,et al.Ribosomal proteins are targets for the NEDD8 pathway.EMBO Rep,2008,9(3):280-286
[29]Loftus SJ,Liu G,Carr SM,et al.Neddylation regulates E2F-1-dependent transcription.EMBO Rep,2012,13(9):811-818
[30]Park HS,Ju UI,Park JW,et al.PPARgamma neddylation essential for adipogenesis is a potential target for treating obesity.Cell Death Differ,2016,23(8):1296-1311
[31]Jayabalan AK,Sanchez A,Park RY,et al.NEDDylation promotes stress granule assembly.Nat Commun,2016,7:12125
[32]Kuriu T,Inoue A,Bito H,et al.Differential control of postsynaptic density scaffolds via actin-dependent and-independent mechanisms.J Neurosci,2006,26(29):7693-7706
[33]Vallejo D,Codocedo JF,Inestrosa NC.Posttranslational modifications regulate the postsynaptic localization of PSD-95.Mol Neurobiol,2017,54(3):1759-1776
[34]Zhang T,Ye Z,Yang X,et al.Neddylation of PB2 reduces its stability and blocks the replication of influenza a virus.Sci Rep,2017,7:43691
[35]Petroski MD,Deshaies RJ.Function and regulation of cullin-RING ubiquitin ligases.Nat Rev Mol Cell Biol,2005,6(1):9-20
[36]Lipkowitz S,Weissman AM.RINGs of good and evil:RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis.Nat Rev Cancer,2011,11(9):629-643
[37]Watson IR,Li BK,Roche O,et al.Chemotherapy induces NEDP1-mediated destabilization of MDM2.Oncogene,2010,29(2):297-304
[38]Abida WM,Nikolaev A,Zhao W,et al.FBXO11 promotes the Neddylation of p53 and inhibits its transcriptional activity.J Biol Chem,2007,282(3):1797-1804
[39]Russell RC,Ohh M.NEDD8 acts as a'molecular switch defining the functional selectivity of VHL.EMBO Rep,2008,9(5):486-491
[40]Watson IR,Blanch A,Lin DC,et al.Mdm2-mediated NEDD8 modification of TAp73 regulates its transactivation function.J Biol Chem,2006,281(45):34096-34103
[41]Oved S,Mosesson Y,Zwang Y,et al.Conjugation to Nedd8 instigates ubiquitylation and down-regulation of activated receptor tyrosine kinases.J Biol Chem,2006,281(31):21640-21651
[42]Lee MR,Lee D,Shin SK,et al.Inhibition of APP intracellular domain(AICD)transcriptional activity via covalent conjugation with Nedd8.Biochem Biophys Res Commun,2008,366(4):976-981
[43]Nagano T,Hashimoto T,Nakashima A,et al.X-linked inhibitor of apoptosis protein mediates neddylation by itself but does not function as a NEDD8-E3 ligase for caspase-7.FEBS Lett,2012,586(11):1612-1616
[44]Ryu JH,Li SH,Park HS,et al.Hypoxia-inducible factor alpha subunit stabilization by NEDD8 conjugation is reactive oxygen species-dependent.J Biol Chem,2011,286(9):6963-6970
[45]Mahata B,Sundqvist A,Xirodimas DP.Recruitment of RPL11 at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and in an Mdm2-dependent manner.Oncogene,2012,31(25):3060-3071
[46]Choo YS,Vogler G,Wang D,et al.Regulation of parkin and PINK1 by neddylation.Hum Mol Genet,2012,21(11):2514-2523
[47]Chen Y,Neve RL,Liu H.Neddylation dysfunction in Alzheimer's disease.J Cell Mol Med,2012,16(11):2583-2591
[48]Leidecker O,Matic I,Mahata B,et al.The ubiquitin E1enzyme Ube1 mediates NEDD8 activation under diverse stress conditions.Cell Cycle,2012,11(6):1142-1150
[49]Singh RK,Zerath S,Kleifeld O,et al.Recognition and cleavage of related to ubiquitin 1(Rub1)and Rub1-ubiquitin chains by components of the ubiquitin-proteasome system.Mol Cell Proteomics,2012,11(12):1595-1611
[50]Embade N,Fernandez-Ramos D,Varela-Rey M,et al.Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through Neddylation.Hepatology,2012,55(4):1237-1248
[51]Noh EH,Hwang HS,Hwang HS,et al.Covalent NEDD8conjugation increases RCAN1 protein stability and potentiates its inhibitory action on calcineurin.PLoS One,2012,7(10):e48315
[52]Zhang J,Bai D,Ma X,et al.hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling Neddylation of ribosomal protein S14.Oncogene,2014,33(2):246-254
[53]Jin HS,Liao L,Park Y,et al.Neddylation pathway regulates T-cell function by targeting an adaptor protein Shc and a protein kinase Erk signaling.Proc Natl Acad Sci USA,2013,110(2):624-629
[54]Zuo W,Huang F,Chiang YJ,et al.c-Cbl-mediated neddylation antagonizes ubiquitination and degradation of the TGF-beta type II receptor.Mol Cell,2013,49(3):499-510
[55]Takashima O,Tsuruta F,Kigoshi Y,et al.Brap2 regulates temporal control of NF-kappaB localization mediated by inflammatory response.PLoS One,2013,8(3):e58911
[56]Brown JS,Lukashchuk N,Sczaniecka-Clift M,et al.Neddylation promotes ubiquitylation and release of Ku from DNA-damage sites.Cell Rep,2015,11(5):704-714
[57]Yan F,Guan J,Peng Y,et al.MyD88 Neddylation negatively regulates MyD88-dependent NF-kappaB signaling through antagonizing its ubiquitination.Biochem Biophys Res Commun,2017,482(4):632-637
[58]Coleman KE,Bekes M,Chapman JR,et al.SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin-RING ubiquitin ligase function.Elife,2017,6:e24325
[59]Lyapina S,Cope G,Shevchenko A,et al.Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.Science,2001,292(5520):1382-1385
[60]Cope GA,Suh GS,Aravind L,et al.Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8from Cul1.Science,2002,298(5593):608-611
[61]Seeger M,Gordon C,Dubiel W.Protein stability:the COP9 signalosome gets in on the act.Curr Biol,2001,11(16):R643-R646
[62]Lingaraju GM,Bunker RD,Cavadini S,et al.Crystal structure of the human COP9 signalosome.Nature,2014,512(7513):161-165
[63]Cavadini S,Fischer ES,Bunker RD,et al.Cullin-RINGubiquitin E3 ligase regulation by the COP9 signalosome.Nature,2016,531(7596):598-603
[64]Kim K,Yoon J,Yim J,et al.Deneddylase 1 regulates deneddylase activity of the Cop9 signalosome in Drosophila melanogaster.Insect Sci,2017,24(1):27-34
[65]Chan Y,Yoon J,Wu J T,et al.DEN1 deneddylates non-cullin proteins in vivo.J Cell Sci,2008,121(Pt 19):3218-3223
[66]Shen LN,Liu H,Dong C,et al.Structural basis of NEDD8 ubiquitin discrimination by the deNeddylating enzyme NEDP1.EMBO J,2005,24(7):1341-1351
[67]Whitby FG,Xia G,Pickart CM,et al.Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes.J Biol Chem,1998,273(52):34983-34991
[68]Mergner J,Heinzlmeir S,Kuster B,et al.Deneddylase1deconjugates NEDD8 from non-cullin protein substrates in Arabidopsis thaliana.Plant Cell,2015,27(3):741-753
[69]Bode AM,Dong Z.Post-translational modification of p53 in tumorigenesis.Nat Rev Cancer,2004,4(10):793-805
[70]Qin H,Wang J,Liang Y,et al.RING1 inhibits transactivation of RBP-J by Notch through interaction with LIMprotein KyoT2.Nucleic Acids Res,2004,32(4):1492-1501
[71]Semenza GL.HIF-1 and mechanisms of hypoxia sensing.Curr Opin Cell Biol,2001,13(2):167-171
[72]Semenza GL.Life with oxygen.Science,2007,318(5847):62-64
[73]Nam SY,Ko YS,Jung J,et al.A hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear factor-kappaB promotes gastric tumour growth and angiogenesis.Br J Cancer,2011,104(1):166-174
[74]Baker RG,Hayden MS,Ghosh S.NF-kappaB,inflammation,and metabolic disease.Cell Metab,2011,13(1):11-22
[75]Hayden MS,Ghosh S.Shared principles in NF-kappaBsignaling.Cell,2008,132(3):344-362
[76]Barnes PJ,Karin M.Nuclear factor-kappaB:a pivotal transcription factor in chronic inflammatory diseases.NEngl J Med,1997,336(15):1066-1071
[77]Li Q,Withoff S,Verma IM.Inflammation-associated cancer:NF-kappaB is the lynchpin.Trends Immunol,2005,26(6):318-325
[78]Walmsley SR,Print C,Farahi N,et al.Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity.J Exp Med,2005,201(1):105-115
[79]Belaiba RS,Bonello S,Zahringer C,et al.Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery smooth muscle cells.Mol Biol Cell,2007,18(12):4691-4697
[80]Guan J,Yu S,Zheng X.Neddylation antagonizes ubiquitination of proliferating cell nuclear antigen and regulates the recruitment of polymerase eta in response to oxidative DNA damage.Protein Cell,2018,9(4):365-379
[81]Paunu N,Lahermo P,Onkamo P,et al.A novel low-penetrance locus for familial glioma at 15q23-q26.3.Cancer Res,2002,62(13):3798-3802
[82]Koschny R,Holland H,Koschny T,et al.Comparative genomic hybridization pattern of non-anaplastic and anaplastic oligodendrogliomas--a meta-analysis.Pathol Res Pract,2006,202(1):23-30
[83]Huang HY,West RB,Tzeng CC,et al.Immunohistochemical and biogenetic features of diffuse-type tenosynovial giant cell tumors:the potential roles of cyclin A,P53,and deletion of 15q in sarcomatous transformation.Clin Cancer Res,2008,14(19):6023-6032
[84]Suzuki H,Ouchida M,Yamamoto H,et al.Decreased expression of the SIN3A gene,a candidate tumor suppressor located at the prevalent allelic loss region15q23 in non-small cell lung cancer.Lung Cancer,2008,59(1):24-31
[85]Soucy TA,Smith PG,Milhollen MA,et al.An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer.Nature,2009,458(7239):732-736
[86]Brownell JE,Sintchak MD,Gavin JM,et al.Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes:the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.Mol Cell,2010,37(1):102-111
[87]Luo Z,Yu G,Lee HW,et al.The Nedd8-activating enzyme inhibitor MLN4924 induces autophagy and apoptosis to suppress liver cancer cell growth.Cancer Res,2012,72(13):3360-3371
[88]Soucy TA,Smith PG,Rolfe M.Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer.Clin Cancer Res,2009,15(12):3912-3916
[89]Zhou L,Zhang W,Sun Y,et al.Protein neddylation and its alterations in human cancers for targeted therapy.Cell Signal,2018,44:92-102
[90]Vanderdys V,Allak A,Guessous F,et al.The neddylation inhibitor pevonedistat(MLN4924)suppresses and radiosensitizes head and neck squamous carcinoma cells and tumors.Mol Cancer Ther,2018,17(2):368-380