泛素链修饰类型研究进展
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摘要
泛素化修饰的蛋白质底物广泛参与蛋白质降解、胞内蛋白质转运、细胞信号转导、自噬和DNA损伤修复等重要的生物学过程。泛素化修饰包括单泛素化修饰和多泛素化修饰。因泛素分子含有7个赖氨酸残基和1个N端甲硫氨酸残基,多泛素化修饰又可分为同型或异型的多聚泛素化修饰。此外,泛素分子的乙酰化修饰和磷酸化修饰大大增加了泛素链的复杂性。不同泛素链的形成往往依赖泛素连接酶或者去泛素化酶。现综述不同类型的泛素链修饰类型的编辑、识别、去除机制及其生物学功能,并讨论泛素分子自身的乙酰化和磷酸化修饰。
Protein ubiquitination is widely involved in multiple celluar processes, such as protein degradation, intracellular protein trafficking, cellular signaling transduction, autophagy and DNA damage responses. Ubiquitin modification includes monoubiquitination and polyubiquitin modification. Since ubiquitin contains seven lysine residues and one N-terminal methionine residue, the ubiquitin chains are divided into homotypic or heterotypic linkages. In addition, ubiquitin acetylation and phosphorylation improve the complexity of ubiquitin chains. There are a series of ubiquitin ligases and deubiqutinases editing different ubiquitin chains. This review focuses on different ubiquitin linkage types to discuss how they are formed, recognized and erased, and what biological functions they have. The acetylated and phosphorylated ubiquitins are also discussed.
Protein ubiquitination is widely involved in multiple celluar processes, such as protein degradation, intracellular protein trafficking, cellular signaling transduction, autophagy and DNA damage responses. Ubiquitin modification includes monoubiquitination and polyubiquitin modification. Since ubiquitin contains seven lysine residues and one N-terminal methionine residue, the ubiquitin chains are divided into homotypic or heterotypic linkages. In addition, ubiquitin acetylation and phosphorylation improve the complexity of ubiquitin chains. There are a series of ubiquitin ligases and deubiqutinases editing different ubiquitin chains. This review focuses on different ubiquitin linkage types to discuss how they are formed, recognized and erased, and what biological functions they have. The acetylated and phosphorylated ubiquitins are also discussed.
引文
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[29]Wang B,Jie Z,Joo D,et al.TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2signalling.Nature,2017,545:365-9
[30]Xu Z,Pei L,Wang L,et al.Snail1-dependent transcriptional repression of Cezanne2 in hepatocellular carcinoma.Oncogene,2014,33:2836-45
[31]Yamanaka K,Ishikawa H,Megumi Y,et al.Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2.Nat Cell Biol,2003,5:336-40
[32]Kirisako T,Kamei K,Murata S,et al.A ubiquitin ligase complex assembles linear polyubiquitin chains.EMBO J,2006,25:4877-87
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[37]Tokunaga F,Nakagawa T,Nakahara M,et al.SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex.Nature,2011,471:633-6
[38]Gerlach B,Cordier SM,Schmukle AC,et al.Linear ubiquitination prevents inflammation and regulates immune signalling.Nature,2011,471:591-6
[39]Peltzer N,Rieser E,Taraborrelli L,et al.HOIP deficiency causes embryonic lethality by aberrant TNFR1-mediated endothelial cell death.Cell Rep,2014,9:153-65
[40]Hrdinka M,Gyrd-Hansen M.The Met1-linked ubiquitin machinery:emerging themes of(de)regulation.Mol Cell,2017,68:265-80
[41]Komander D,Lord CJ,Scheel H,et al.The structure of the CYLD USP domain explains its specificity for Lys63-linked polyubiquitin and reveals a B box module.Mol Cell,2008,29:451-64
[42]Komander D,Reyes-Turcu F,Licchesi JD,et al.Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains.EMBO Rep,2009,10:466-73
[43]Elliott PR,Leske D,Hrdinka M,et al.SPATA2 links CYLD to LUBAC,activates CYLD,and controls LUBACsignaling.Mol Cell,2016,63:990-1005
[44]Kupka S,De Miguel D,Draber P,et al.SPATA2-mediated binding of CYLD to HOIP enables CYLD recruitment to signaling complexes.Cell Rep,2016,16:2271-80
[45]Schlicher L,Wissler M,Preiss F,et al.SPATA2 promotes CYLD activity and regulates TNF-induced NF-κB signaling and cell death.EMBO Rep,2016,17:1485-97
[46]Wagner SA,Satpathy S,Beli P,et al.SPATA2 links CYLDto the TNF-αreceptor signaling complex and modulates the receptor signaling outcomes.EMBO J,2016,35:1868-84
[47]Elliott PR,Nielsen SV,Marco-Casanova P,et al.Molecular basis and regulation of OTULIN-LUBAC interaction.Mol Cell,2014,54:335-48
[48]Schaeffer V,Akutsu M,Olma MH,et al.Binding of OTULIN to the PUB domain of HOIP controls NF-κBsignaling.Mol Cell,2014,54:349-61
[49]Lork M,Verhelst K,Beyaert R.CYLD,A20 and OTULINdeubiquitinases in NF-κB signaling and cell death:so similar,yet so different.Cell Death Differ,2017,24:1172-83
[50]Rivkin E,Almeida SM,Ceccarelli DF,et al.The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis.Nature,2013,498:318-24
[51]Damgaard RB,Walker JA,Marco-Casanova P,et al.The deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity.Cell,2016,166:1215-30 e20
[52]Draber P,Kupka S,Reichert M,et al.LUBAC-recruited CYLD and A20 regulate gene activation and cell death by exerting opposing effects on linear ubiquitin in signaling complexes.Cell Rep,2015,13:2258-72
[53]Shembade N,Ma A,Harhaj EW.Inhibition of NF-κBsignaling by A20 through disruption of ubiquitin enzyme complexes.Science,2010,327:1135-9
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