1932

Abstract

Ubiquitylation is an essential posttranslational modification that controls cell division, differentiation, and survival in all eukaryotes. By combining multiple E3 ligases (writers), ubiquitin-binding effectors (readers), and de-ubiquitylases (erasers) with functionally distinct ubiquitylation tags, the ubiquitin system constitutes a powerful signaling network that is employed in similar ways from yeast to humans. Here, we discuss conserved principles of ubiquitin-dependent signaling that illustrate how this posttranslational modification shapes intracellular signaling networks to establish robust development and homeostasis throughout the eukaryotic kingdom.

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2018-10-06
2024-04-19
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Literature Cited

  1. Adorno M, Sikandar S, Mitra SS, Kuo A, Nicolis di Robilant B et al. 2013. Usp16 contributes to somatic stem-cell defects in Down's syndrome. Nature 501:380–84
    [Google Scholar]
  2. Almeida M, Pintacuda G, Masui O, Koseki Y, Gdula M et al. 2017. PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation. Science 356:1081–84
    [Google Scholar]
  3. Antonioli M, Albiero F, Nazio F, Vescovo T, Perdomo AB et al. 2014. AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics. Dev. Cell 31:734–46
    [Google Scholar]
  4. Ashida H, Kim M, Schmidt-Supprian M, Ma A, Ogawa M, Sasakawa C 2010. A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKγ to dampen the host NF-κB-mediated inflammatory response. Nat. Cell Biol. 12:66–73 Suppl:1–9
    [Google Scholar]
  5. Atanassov BS, Mohan RD, Lan X, Kuang X, Lu Y et al. 2016. ATXN7L3 and ENY2 coordinate activity of multiple H2B deubiquitinases important for cellular proliferation and tumor growth. Mol. Cell 62:558–71
    [Google Scholar]
  6. Bachofner M, Speicher T, Bogorad RL, Muzumdar S, Derrer CP et al. 2017. Large-scale quantitative proteomics identifies the ubiquitin ligase Nedd4-1 as an essential regulator of liver regeneration. Dev. Cell 42:616–25.e8
    [Google Scholar]
  7. Bengtson MH, Joazeiro CA 2010. Role of a ribosome-associated E3 ubiquitin ligase in protein quality control. Nature 467:470–73
    [Google Scholar]
  8. Berner N, Reutter KR, Wolf DH 2018. Protein quality control of the endoplasmic reticulum and ubiquitin-proteasome-triggered degradation of aberrant proteins: Yeast pioneers the path. Annu. Rev. Biochem. 87:751–82
    [Google Scholar]
  9. Bhogaraju S, Kalayil S, Liu Y, Bonn F, Colby T et al. 2016. Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination. Cell 167:1636–49.e13
    [Google Scholar]
  10. Blackledge NP, Farcas AM, Kondo T, King HW, McGouran JF et al. 2014. Variant PRC1 complex–dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation. Cell 157:1445–59
    [Google Scholar]
  11. Blythe EE, Olson KC, Chau V, Deshaies RJ 2017. Ubiquitin- and ATP-dependent unfoldase activity of P97/VCP·NPLOC4·UFD1L is enhanced by a mutation that causes multisystem proteinopathy. PNAS 114:E4380–88
    [Google Scholar]
  12. Bodnar NO, Rapoport TA 2017. Molecular mechanism of substrate processing by the Cdc48 ATPase complex. Cell 169:722–35.e9
    [Google Scholar]
  13. Boersma V, Moatti N, Segura-Bayona S, Peuscher MH, van der Torre J et al. 2015. MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5′ end resection. Nature 521:537–40
    [Google Scholar]
  14. Bosanac I, Wertz IE, Pan B, Yu C, Kusam S et al. 2010. Ubiquitin binding to A20 ZnF4 is required for modulation of NF-κB signaling. Mol. Cell 40:548–57
    [Google Scholar]
  15. Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC et al. 2012. A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress. Cell 151:1042–54
    [Google Scholar]
  16. Breitschopf K, Bengal E, Ziv T, Admon A, Ciechanover A 1998. A novel site for ubiquitination: The N-terminal residue, and not internal lysines of MyoD, is essential for conjugation and degradation of the protein. EMBO J 17:5964–73
    [Google Scholar]
  17. Butkinaree C, Guo L, Ramkhelawon B, Wanschel A, Brodsky JL et al. 2014. A regulator of secretory vesicle size, Kelch-like protein 12, facilitates the secretion of apolipoprotein B100 and very-low-density lipoproteins—brief report. Arterioscler. Thromb. Vasc. Biol. 34:251–54
    [Google Scholar]
  18. Cadwell K, Coscoy L 2005. Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase. Science 309:127–30
    [Google Scholar]
  19. Cao R, Tsukada Y, Zhang Y 2005. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol. Cell 20:845–54
    [Google Scholar]
  20. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H et al. 2002. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298:1039–43
    [Google Scholar]
  21. Chau V, Tobias JW, Bachmair A, Marriott D, Ecker DJ et al. 1989. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243:1576–83
    [Google Scholar]
  22. Chu J, Hong NA, Masuda CA, Jenkins BV, Nelms KA et al. 2009. A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration. PNAS 106:2097–103
    [Google Scholar]
  23. Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ et al. 2001. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat. Cell Biol. 3:93–96
    [Google Scholar]
  24. Cooper S, Dienstbier M, Hassan R, Schermelleh L, Sharif J et al. 2014. Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment. Cell Rep 7:1456–70
    [Google Scholar]
  25. Cunningham CN, Baughman JM, Phu L, Tea JS, Yu C et al. 2015. USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria. Nat. Cell Biol. 17:160–69
    [Google Scholar]
  26. Damgaard RB, Walker JA, Marco-Casanova P, Morgan NV, Titheradge HL et al. 2016. The deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity. Cell 166:1215–30.e20
    [Google Scholar]
  27. Davey NE, Morgan DO 2016. Building a regulatory network with short linear sequence motifs: lessons from the degrons of the anaphase-promoting complex. Mol. Cell 64:12–23
    [Google Scholar]
  28. de Jong MF, Liu Z, Chen D, Alto NM 2016. Shigella flexneri suppresses NF-κB activation by inhibiting linear ubiquitin chain ligation. Nat. Microbiol. 1:16084
    [Google Scholar]
  29. Deng L, Wang C, Spencer E, Yang L, Braun A et al. 2000. Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103:351–61
    [Google Scholar]
  30. Deshaies RJ, Joazeiro CA 2009. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 78:399–434
    [Google Scholar]
  31. Djuzenova CS, Zimmermann M, Katzer A, Fiedler V, Distel LV et al. 2015. A prospective study on histone γ-H2AX and 53BP1 foci expression in rectal carcinoma patients: correlation with radiation therapy–induced outcome. BMC Cancer 15:856
    [Google Scholar]
  32. Dobzinski N, Chuartzman SG, Kama R, Schuldiner M, Gerst JE 2015. Starvation-dependent regulation of Golgi quality control links the TOR signaling and vacuolar protein sorting pathways. Cell Rep 12:1876–86
    [Google Scholar]
  33. Doil C, Mailand N, Bekker-Jensen S, Menard P, Larsen DH et al. 2009. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell 136:435–46
    [Google Scholar]
  34. Elia AE, Wang DC, Willis NA, Boardman AP, Hajdu I et al. 2015. RFWD3-dependent ubiquitination of RPA regulates repair at stalled replication forks. Mol. Cell 60:280–93
    [Google Scholar]
  35. Elliott PR, Leske D, Hrdinka M, Bagola K, Fiil BK et al. 2016. SPATA2 links CYLD to LUBAC, activates CYLD, and controls LUBAC signaling. Mol. Cell 63:990–1005
    [Google Scholar]
  36. Elliott PR, Nielsen SV, Marco-Casanova P, Fiil BK, Keusekotten K et al. 2014. Molecular basis and regulation of OTULIN-LUBAC interaction. Mol. Cell 54:335–48
    [Google Scholar]
  37. Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L et al. 2011. Global identification of modular Cullin-RING ligase substrates. Cell 147:459–74
    [Google Scholar]
  38. Emmerich CH, Bakshi S, Kelsall IR, Ortiz-Guerrero J, Shpiro N, Cohen P 2016. Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling. Biochem. Biophys. Res. Commun. 474:452–61
    [Google Scholar]
  39. Emmerich CH, Ordureau A, Strickson S, Arthur JS, Pedrioli PG et al. 2013. Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. PNAS 110:15247–52
    [Google Scholar]
  40. Fiskin E, Bionda T, Dikic I, Behrends C 2016. Global analysis of host and bacterial ubiquitinome in response to Salmonella Typhimurium infection. Mol. Cell 62:967–81
    [Google Scholar]
  41. Fradet-Turcotte A, Canny MD, Escribano-Diaz C, Orthwein A, Leung CC et al. 2013. 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark. Nature 499:50–54
    [Google Scholar]
  42. Frankel EB, Audhya A 2018. ESCRT-dependent cargo sorting at multivesicular endosomes. Semin. Cell Dev. Biol. 74:4–10
    [Google Scholar]
  43. Fuchs G, Shema E, Vesterman R, Kotler E, Wolchinsky Z et al. 2012. RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation. Mol. Cell 46:662–73
    [Google Scholar]
  44. Gao Z, Zhang J, Bonasio R, Strino F, Sawai A et al. 2012. PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Mol. Cell 45:344–56
    [Google Scholar]
  45. Gardner RG, Nelson ZW, Gottschling DE 2005. Degradation-mediated protein quality control in the nucleus. Cell 120:803–15
    [Google Scholar]
  46. Geffen Y, Appleboim A, Gardner RG, Friedman N, Sadeh R, Ravid T 2016. Mapping the landscape of a eukaryotic degronome. Mol. Cell 63:1055–65
    [Google Scholar]
  47. Gersch M, Gladkova C, Schubert AF, Michel MA, Maslen S, Komander D 2017. Mechanism and regulation of the Lys6-selective deubiquitinase USP30. Nat. Struct. Mol. Biol. 24:920–30
    [Google Scholar]
  48. Glinsky GV 2006. Genomic models of metastatic cancer: functional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG) protein chromatin silencing pathway. Cell Cycle 5:1208–16
    [Google Scholar]
  49. Goldknopf IL, French MF, Musso R, Busch H 1977. Presence of protein A24 in rat liver nucleosomes. PNAS 74:5492–95
    [Google Scholar]
  50. Gorur A, Yuan L, Kenny SJ, Baba S, Xu K, Schekman R 2017. COPII-coated membranes function as transport carriers of intracellular procollagen I. J. Cell Biol. 216:1745–59
    [Google Scholar]
  51. Gudjonsson T, Altmeyer M, Savic V, Toledo L, Dinant C et al. 2012. TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes. Cell 150:697–709
    [Google Scholar]
  52. Harper JW, Ordureau A, Heo JM 2018. Building and decoding ubiquitin chains for mitophagy. Nat. Rev. Mol. Cell Biol. 19:93–108
    [Google Scholar]
  53. Harrigan JA, Jacq X, Martin NM, Jackson SP 2018. Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat. Rev. Drug Discov. 17:57–78
    [Google Scholar]
  54. Heck JW, Cheung SK, Hampton RY 2010. Cytoplasmic protein quality control degradation mediated by parallel actions of the E3 ubiquitin ligases Ubr1 and San1. PNAS 107:1106–11
    [Google Scholar]
  55. Hessa T, Sharma A, Mariappan M, Eshleman HD, Gutierrez E, Hegde RS 2011. Protein targeting and degradation are coupled for elimination of mislocalized proteins. Nature 475:394–97
    [Google Scholar]
  56. Higgins R, Gendron JM, Rising L, Mak R, Webb K et al. 2015. The unfolded protein response triggers site-specific regulatory ubiquitylation of 40S ribosomal proteins. Mol. Cell 59:35–49
    [Google Scholar]
  57. Hirano S, Kawasaki M, Ura H, Kato R, Raiborg C et al. 2006. Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting. Nat. Struct. Mol. Biol. 13:272–77
    [Google Scholar]
  58. Hjerpe R, Bett JS, Keuss MJ, Solovyova A, McWilliams TG et al. 2016. UBQLN2 mediates autophagy-independent protein aggregate clearance by the proteasome. Cell 166:935–49
    [Google Scholar]
  59. Hrdinka M, Gyrd-Hansen M 2017. The Met1-linked ubiquitin machinery: emerging themes of (de)regulation. Mol. Cell 68:265–80
    [Google Scholar]
  60. Hu Y, Scully R, Sobhian B, Xie A, Shestakova E, Livingston DM 2011. RAP80-directed tuning of BRCA1 homologous recombination function at ionizing radiation–induced nuclear foci. Genes Dev 25:685–700
    [Google Scholar]
  61. Huen MS, Grant R, Manke I, Minn K, Yu X et al. 2007. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131:901–14
    [Google Scholar]
  62. Hwang CS, Shemorry A, Auerbach D, Varshavsky A 2010. The N-end rule pathway is mediated by a complex of the RING-type Ubr1 and HECT-type Ufd4 ubiquitin ligases. Nat. Cell Biol. 12:1177–85
    [Google Scholar]
  63. Illingworth RS, Moffat M, Mann AR, Read D, Hunter CJ et al. 2015. The E3 ubiquitin ligase activity of RING1B is not essential for early mouse development. Genes Dev 29:1897–902
    [Google Scholar]
  64. Ishikawa T, Toyama T, Nakamura Y, Tamada K, Shimizu H et al. 2017. UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage–specific manner. J. Cell Biol. 216:1761–74
    [Google Scholar]
  65. Ishiyama S, Nishiyama A, Saeki Y, Moritsugu K, Morimoto D et al. 2017. Structure of the Dnmt1 reader module complexed with a unique two-mono-ubiquitin mark on histone H3 reveals the basis for DNA methylation maintenance. Mol. Cell 68:350–60.e7
    [Google Scholar]
  66. Ismail IH, Gagne JP, Genois MM, Strickfaden H, McDonald D et al. 2015. The RNF138 E3 ligase displaces Ku to promote DNA end resection and regulate DNA repair pathway choice. Nat. Cell Biol. 17:1446–57
    [Google Scholar]
  67. Itakura E, Zavodszky E, Shao S, Wohlever ML, Keenan RJ, Hegde RS 2016. Ubiquilins chaperone and triage mitochondrial membrane proteins for degradation. Mol. Cell 63:21–33
    [Google Scholar]
  68. Jin L, Pahuja KB, Wickliffe KE, Gorur A, Baumgartel C et al. 2012. Ubiquitin-dependent regulation of COPII coat size and function. Nature 482:495–500
    [Google Scholar]
  69. Jin L, Williamson A, Banerjee S, Philipp I, Rape M 2008. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133:653–65
    [Google Scholar]
  70. Kaelin WG 2007. Von Hippel–Lindau disease. Annu. Rev. Pathol. 2:145–73
    [Google Scholar]
  71. Kalb R, Latwiel S, Baymaz HI, Jansen PW, Muller CW et al. 2014. Histone H2A monoubiquitination promotes histone H3 methylation in Polycomb repression. Nat. Struct. Mol. Biol. 21:569–71
    [Google Scholar]
  72. Kanayama A, Seth RB, Sun L, Ea CK, Hong M et al. 2004. TAB2 and TAB3 activate the NF-κB pathway through binding to polyubiquitin chains. Mol. Cell 15:535–48
    [Google Scholar]
  73. Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K et al. 2014. PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J. Cell Biol. 205:143–53
    [Google Scholar]
  74. Kategaya L, Di Lello P, Rouge L, Pastor R, Clark KR et al. 2017. USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature 550:534–38
    [Google Scholar]
  75. Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS et al. 2014. Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem. J. 460:127–39
    [Google Scholar]
  76. Keszei AF, Sicheri F 2017. Mechanism of catalysis, E2 recognition, and autoinhibition for the IpaH family of bacterial E3 ubiquitin ligases. PNAS 114:1311–16
    [Google Scholar]
  77. Keusekotten K, Elliott PR, Glockner L, Fiil BK, Damgaard RB et al. 2013. OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell 153:1312–26
    [Google Scholar]
  78. Kim H, Chen J, Yu X 2007. Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 316:1202–5
    [Google Scholar]
  79. Kim HK, Kim RR, Oh JH, Cho H, Varshavsky A, Hwang CS 2014. The N-terminal methionine of cellular proteins as a degradation signal. Cell 156:158–69
    [Google Scholar]
  80. Kim J, Hake SB, Roeder RG 2005. The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activator interactions. Mol. Cell 20:759–70
    [Google Scholar]
  81. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J et al. 2011. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell 44:325–40
    [Google Scholar]
  82. Kolas NK, Chapman JR, Nakada S, Ylanko J, Chahwan R et al. 2007. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318:1637–40
    [Google Scholar]
  83. Komander D, Reyes-Turcu F, Licchesi JD, Odenwaelder P, Wilkinson KD, Barford D 2009. Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Rep 10:466–73
    [Google Scholar]
  84. Kostova KK, Hickey KL, Osuna BA, Hussmann JA, Frost A et al. 2017. CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptides. Science 357:414–17
    [Google Scholar]
  85. Kotewicz KM, Ramabhadran V, Sjoblom N, Vogel JP, Haenssler E et al. 2017. A single Legionella effector catalyzes a multistep ubiquitination pathway to rearrange tubular endoplasmic reticulum for replication. Cell Host Microbe 21:169–81
    [Google Scholar]
  86. Koyano F, Okatsu K, Kosako H, Tamura Y, Go E et al. 2014. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510:162–66
    [Google Scholar]
  87. Kristariyanto YA, Abdul Rehman SA, Campbell DG, Morrice NA, Johnson C et al. 2015. K29-selective ubiquitin binding domain reveals structural basis of specificity and heterotypic nature of K29 polyubiquitin. Mol. Cell 58:83–94
    [Google Scholar]
  88. Kupka S, De Miguel D, Draber P, Martino L, Surinova S et al. 2016. SPATA2-mediated binding of CYLD to HOIP enables CYLD recruitment to signaling complexes. Cell Rep 16:2271–80
    [Google Scholar]
  89. Lan X, Atanassov BS, Li W, Zhang Y, Florens L et al. 2016. USP44 is an integral component of N-CoR that contributes to gene repression by deubiquitinating histone H2B. Cell Rep 17:2382–93
    [Google Scholar]
  90. Laplantine E, Fontan E, Chiaravalli J, Lopez T, Lakisic G et al. 2009. NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain. EMBO J 28:2885–95
    [Google Scholar]
  91. Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C et al. 2015. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:309–14
    [Google Scholar]
  92. Lee JG, Takahama S, Zhang G, Tomarev SI, Ye Y 2016. Unconventional secretion of misfolded proteins promotes adaptation to proteasome dysfunction in mammalian cells. Nat. Cell Biol. 18:765–76
    [Google Scholar]
  93. Levine SS, Weiss A, Erdjument-Bromage H, Shao Z, Tempst P, Kingston RE 2002. The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans. Mol. Cell. Biol. 22:6070–78
    [Google Scholar]
  94. Levkowitz G, Waterman H, Zamir E, Kam Z, Oved S et al. 1998. c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. Genes Dev 12:3663–74
    [Google Scholar]
  95. Lin CH, MacGurn JA, Chu T, Stefan CJ, Emr SD 2008. Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface. Cell 135:714–25
    [Google Scholar]
  96. Lin HC, Ho SC, Chen YY, Khoo KH, Hsu PH, Yen HC 2015. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding. Science 349:91–95
    [Google Scholar]
  97. Liu C, Liu W, Ye Y, Li W 2017. Ufd2p synthesizes branched ubiquitin chains to promote the degradation of substrates modified with atypical chains. Nat. Commun. 8:14274
    [Google Scholar]
  98. Liu CC, Lin YC, Chen YH, Chen CM, Pang LY et al. 2016. Cul3-KLHL20 ubiquitin ligase governs the turnover of ULK1 and VPS34 complexes to control autophagy termination. Mol. Cell 61:84–97
    [Google Scholar]
  99. Lyumkis D, Oliveira dos Passos D, Tahara EB, Webb K, Bennett EJ et al. 2014. Structural basis for translational surveillance by the large ribosomal subunit–associated protein quality control complex. PNAS 111:15981–86
    [Google Scholar]
  100. MacGurn JA, Hsu PC, Smolka MB, Emr SD 2011. TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor. Cell 147:1104–17
    [Google Scholar]
  101. Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J et al. 2007. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131:887–900
    [Google Scholar]
  102. Manzanillo PS, Ayres JS, Watson RO, Collins AC, Souza G et al. 2013. The ubiquitin ligase parkin mediates resistance to intracellular pathogens. Nature 501:512–16
    [Google Scholar]
  103. Marechal A, Li JM, Ji XY, Wu CS, Yazinski SA et al. 2014. PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry. Mol. Cell 53:235–46
    [Google Scholar]
  104. Mattiroli F, Vissers JH, van Dijk WJ, Ikpa P, Citterio E et al. 2012. RNF168 ubiquitinates K13–15 on H2A/H2AX to drive DNA damage signaling. Cell 150:1182–95
    [Google Scholar]
  105. McCullough J, Clague MJ, Urbe S 2004. AMSH is an endosome-associated ubiquitin isopeptidase. J. Cell Biol. 166:487–92
    [Google Scholar]
  106. McGinty RK, Henrici RC, Tan S 2014. Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature 514:591–96
    [Google Scholar]
  107. McGourty CA, Akopian D, Walsh C, Gorur A, Werner A et al. 2016. Regulation of the CUL3 ubiquitin ligase by a calcium-dependent co-adaptor. Cell 167:525–38.e14
    [Google Scholar]
  108. Mevissen TET, Komander D 2017. Mechanisms of deubiquitinase specificity and regulation. Annu. Rev. Biochem. 86:159–92
    [Google Scholar]
  109. Meyer HJ, Rape M 2014. Enhanced protein degradation by branched ubiquitin chains. Cell 157:910–21
    [Google Scholar]
  110. Michel MA, Swatek KN, Hospenthal MK, Komander D 2017. Ubiquitin linkage–specific affimers reveal insights into K6-linked ubiquitin signaling. Mol. Cell 68:233–46.e5
    [Google Scholar]
  111. Mischerikow N, Heck AJ 2011. Targeted large-scale analysis of protein acetylation. Proteomics 11:571–89
    [Google Scholar]
  112. Mizuno E, Kawahata K, Kato M, Kitamura N, Komada M 2003. STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif. Mol. Biol. Cell 14:3675–89
    [Google Scholar]
  113. Nakada S, Tai I, Panier S, Al-Hakim A, Iemura S et al. 2010. Non-canonical inhibition of DNA damage–dependent ubiquitination by OTUB1. Nature 466:941–46
    [Google Scholar]
  114. Narendra D, Tanaka A, Suen DF, Youle RJ 2008. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 183:795–803
    [Google Scholar]
  115. Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA et al. 2010. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLOS Biol 8:e1000298
    [Google Scholar]
  116. Nguyen AT, Prado MA, Schmidt PJ, Sendamarai AK, Wilson-Grady JT et al. 2017. UBE2O remodels the proteome during terminal erythroid differentiation. Science 357:eaan0218
    [Google Scholar]
  117. Nishiyama A, Yamaguchi L, Sharif J, Johmura Y, Kawamura T et al. 2013. Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication. Nature 502:249–53
    [Google Scholar]
  118. Noad J, von der Malsburg A, Pathe C, Michel MA, Komander D, Randow F 2017. LUBAC-synthesized linear ubiquitin chains restrict cytosol-invading bacteria by activating autophagy and NF-κB. Nat. Microbiol. 2:17063
    [Google Scholar]
  119. Ohtake F, Saeki Y, Ishido S, Kanno J, Tanaka K 2016. The K48-K63 branched ubiquitin chain regulates NF-κB signaling. Mol. Cell 64:251–66
    [Google Scholar]
  120. Ohtake F, Tsuchiya H, Saeki Y, Tanaka K 2018. K63 ubiquitylation triggers proteasomal degradation by seeding branched ubiquitin chains. PNAS In press
  121. Okamoto K, Bartocci C, Ouzounov I, Diedrich JK, Yates JR3rd, Denchi EL 2013. A two-step mechanism for TRF2-mediated chromosome-end protection. Nature 494:502–5
    [Google Scholar]
  122. Ordureau A, Heo JM, Duda DM, Paulo JA, Olszewski JL et al. 2015. Defining roles of PARKIN and ubiquitin phosphorylation by PINK1 in mitochondrial quality control using a ubiquitin replacement strategy. PNAS 112:6637–42
    [Google Scholar]
  123. Ordureau A, Sarraf SA, Duda DM, Heo JM, Jedrychowski MP et al. 2014. Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol. Cell 56:360–75
    [Google Scholar]
  124. Orthwein A, Fradet-Turcotte A, Noordermeer SM, Canny MD, Brun CM et al. 2014. Mitosis inhibits DNA double-strand break repair to guard against telomere fusions. Science 344:189–93
    [Google Scholar]
  125. Orthwein A, Noordermeer SM, Wilson MD, Landry S, Enchev RI et al. 2015. A mechanism for the suppression of homologous recombination in G1 cells. Nature 528:422–26
    [Google Scholar]
  126. Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP et al. 2007. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447:859–63
    [Google Scholar]
  127. Panier S, Ichijima Y, Fradet-Turcotte A, Leung CC, Kaustov L et al. 2012. Tandem protein interaction modules organize the ubiquitin-dependent response to DNA double-strand breaks. Mol. Cell 47:383–95
    [Google Scholar]
  128. Pao KC, Wood NT, Knebel A, Rafie K, Stanley M et al. 2018. Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity. Nature 556:381–85
    [Google Scholar]
  129. Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I et al. 2014. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature 507:508–12
    [Google Scholar]
  130. Pavri R, Zhu B, Li G, Trojer P, Mandal S et al. 2006. Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell 125:703–17
    [Google Scholar]
  131. Pengelly AR, Kalb R, Finkl K, Muller J 2015. Transcriptional repression by PRC1 in the absence of H2A monoubiquitylation. Genes Dev 29:1487–92
    [Google Scholar]
  132. Pierce NW, Kleiger G, Shan SO, Deshaies RJ 2009. Detection of sequential polyubiquitylation on a millisecond timescale. Nature 462:615–19
    [Google Scholar]
  133. Polajnar M, Dietz MS, Heilemann M, Behrends C 2017. Expanding the host cell ubiquitylation machinery targeting cytosolic Salmonella. . EMBO Rep 18:1572–85
    [Google Scholar]
  134. Polo S, Sigismund S, Faretta M, Guidi M, Capua MR et al. 2002. A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins. Nature 416:451–55
    [Google Scholar]
  135. Prudden J, Pebernard S, Raffa G, Slavin DA, Perry JJ et al. 2007. SUMO-targeted ubiquitin ligases in genome stability. EMBO J 26:4089–101
    [Google Scholar]
  136. Pruneda JN, Durkin CH, Geurink PP, Ovaa H, Santhanam B et al. 2016. The molecular basis for ubiquitin and ubiquitin-like specificities in bacterial effector proteases. Mol. Cell 63:261–76
    [Google Scholar]
  137. Purvis JE, Lahav G 2013. Encoding and decoding cellular information through signaling dynamics. Cell 152:945–56
    [Google Scholar]
  138. Qiao R, Weissmann F, Yamaguchi M, Brown NG, VanderLinden R et al. 2016. Mechanism of APC/CCDC20 activation by mitotic phosphorylation. PNAS 113:E2570–78
    [Google Scholar]
  139. Qin W, Wolf P, Liu N, Link S, Smets M et al. 2015. DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination. Cell Res 25:911–29
    [Google Scholar]
  140. Qiu J, Sheedlo MJ, Yu K, Tan Y, Nakayasu ES et al. 2016. Ubiquitination independent of E1 and E2 enzymes by bacterial effectors. Nature 533:120–24
    [Google Scholar]
  141. Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N et al. 2009. Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation. Cell 136:1098–109
    [Google Scholar]
  142. Rape M 2017. Ubiquitylation at the crossroads of development and disease. Nat. Rev. Mol. Cell Biol. 19:59–70
    [Google Scholar]
  143. Rape M, Hoppe T, Gorr I, Kalocay M, Richly H, Jentsch S 2001. Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48UFD1/NPL4, a ubiquitin-selective chaperone. Cell 107:667–77
    [Google Scholar]
  144. Rape M, Reddy SK, Kirschner MW 2006. The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell 124:89–103
    [Google Scholar]
  145. Rivkin E, Almeida SM, Ceccarelli DF, Juang YC, MacLean TA et al. 2013. The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis. Nature 498:318–24
    [Google Scholar]
  146. Rodrigo-Brenni MC, Gutierrez E, Hegde RS 2014. Cytosolic quality control of mislocalized proteins requires RNF126 recruitment to Bag6. Mol. Cell 55:227–37
    [Google Scholar]
  147. Rosenbaum JC, Fredrickson EK, Oeser ML, Garrett-Engele CM, Locke MN et al. 2011. Disorder targets misorder in nuclear quality control degradation: A disordered ubiquitin ligase directly recognizes its misfolded substrates. Mol. Cell 41:93–106
    [Google Scholar]
  148. Rousseau A, Bertolotti A 2016. An evolutionarily conserved pathway controls proteasome homeostasis. Nature 536:184–89
    [Google Scholar]
  149. Sanada T, Kim M, Mimuro H, Suzuki M, Ogawa M et al. 2012. The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response. Nature 483:623–26
    [Google Scholar]
  150. Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL et al. 2013. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 496:372–76
    [Google Scholar]
  151. Savio MG, Wollscheid N, Cavallaro E, Algisi V, Di Fiore PP et al. 2016. USP9X controls EGFR fate by deubiquitinating the endocytic adaptor Eps15. Curr. Biol. 26:173–83
    [Google Scholar]
  152. Scheffner M, Huibregtse JM, Vierstra RD, Howley PM 1993. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75:495–505
    [Google Scholar]
  153. Scheuermann JC, de Ayala Alonso AG, Oktaba K, Ly-Hartig N, McGinty RK et al. 2010. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465:243–47
    [Google Scholar]
  154. Schmidt CK, Galanty Y, Sczaniecka-Clift M, Coates J, Jhujh S et al. 2015. Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair. Nat. Cell Biol. 17:1458–70
    [Google Scholar]
  155. Schubert AF, Gladkova C, Pardon E, Wagstaff JL, Freund SMV et al. 2017. Structure of PINK1 in complex with its substrate ubiquitin. Nature 552:51–56
    [Google Scholar]
  156. Shao S, Brown A, Santhanam B, Hegde RS 2015. Structure and assembly pathway of the ribosome quality control complex. Mol. Cell 57:433–44
    [Google Scholar]
  157. Shao S, Rodrigo-Brenni MC, Kivlen MH, Hegde RS 2017. Mechanistic basis for a molecular triage reaction. Science 355:298–302
    [Google Scholar]
  158. Shao S, von der Malsburg K, Hegde RS 2013. Listerin-dependent nascent protein ubiquitination relies on ribosome subunit dissociation. Mol. Cell 50:637–48
    [Google Scholar]
  159. Shemorry A, Hwang CS, Varshavsky A 2013. Control of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway. Mol. Cell 50:540–51
    [Google Scholar]
  160. Shen PS, Park J, Qin Y, Li X, Parsawar K et al. 2015. Protein synthesis. Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains. Science 347:75–78
    [Google Scholar]
  161. Shimizu Y, Okuda-Shimizu Y, Hendershot LM 2010. Ubiquitylation of an ERAD substrate occurs on multiple types of amino acids. Mol. Cell 40:917–26
    [Google Scholar]
  162. Singh R, Cuervo AM 2011. Autophagy in the cellular energetic balance. Cell Metab 13:495–504
    [Google Scholar]
  163. Skaar JR, Pagan JK, Pagano M 2013. Mechanisms and function of substrate recruitment by F-box proteins. Nat. Rev. Mol. Cell Biol. 14:369–81
    [Google Scholar]
  164. Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ 2011. Direct, noncatalytic mechanism of IKK inhibition by A20. Mol. Cell 44:559–71
    [Google Scholar]
  165. Sobhian B, Shao G, Lilli DR, Culhane AC, Moreau LA et al. 2007. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science 316:1198–202
    [Google Scholar]
  166. Sowa ME, Bennett EJ, Gygi SP, Harper JW 2009. Defining the human deubiquitinating enzyme interaction landscape. Cell 138:389–403
    [Google Scholar]
  167. Stewart GS, Panier S, Townsend K, Al-Hakim AK, Kolas NK et al. 2009. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell 136:420–34
    [Google Scholar]
  168. Sung MK, Porras-Yakushi TR, Reitsma JM, Huber FM, Sweredoski MJ et al. 2016. A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins. eLife 5:e19105
    [Google Scholar]
  169. Tawo R, Pokrzywa W, Kevei E, Akyuz ME, Balaji V et al. 2017. The ubiquitin ligase CHIP integrates proteostasis and aging by regulation of insulin receptor turnover. Cell 169:470–82.e13
    [Google Scholar]
  170. Tessadori F, Giltay JC, Hurst JA, Massink MP, Duran K et al. 2017. Germline mutations affecting the histone H4 core cause a developmental syndrome by altering DNA damage response and cell cycle control. Nat. Genet. 49:1642–46
    [Google Scholar]
  171. Thorslund T, Ripplinger A, Hoffmann S, Wild T, Uckelmann M et al. 2015. Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage. Nature 527:389–93
    [Google Scholar]
  172. Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T et al. 2009. Involvement of linear polyubiquitylation of NEMO in NF-κB activation. Nat. Cell Biol. 11:123–32
    [Google Scholar]
  173. Turnbull AP, Ioannidis S, Krajewski WW, Pinto-Fernandez A, Heride C et al. 2017. Molecular basis of USP7 inhibition by selective small-molecule inhibitors. Nature 550:481–86
    [Google Scholar]
  174. Uckelmann M, Densham RM, Baas R, Winterwerp HHK, Fish A et al. 2018. USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A. Nat. Commun. 9:229
    [Google Scholar]
  175. van Wijk SJ, Fiskin E, Putyrski M, Pampaloni F, Hou J et al. 2012. Fluorescence-based sensors to monitor localization and functions of linear and K63-linked ubiquitin chains in cells. Mol. Cell 47:797–809
    [Google Scholar]
  176. van Wijk SJL, Fricke F, Herhaus L, Gupta J, Hotte K et al. 2017. Linear ubiquitination of cytosolic Salmonella Typhimurium activates NF-κB and restricts bacterial proliferation. Nat. Microbiol. 2:17066
    [Google Scholar]
  177. Wang B, Matsuoka S, Ballif BA, Zhang D, Smogorzewska A et al. 2007. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science 316:1194–98
    [Google Scholar]
  178. Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ 2001. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346–51
    [Google Scholar]
  179. Wang F, Durfee LA, Huibregtse JM 2013. A cotranslational ubiquitination pathway for quality control of misfolded proteins. Mol. Cell 50:368–78
    [Google Scholar]
  180. Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P et al. 2004. Role of histone H2A ubiquitination in Polycomb silencing. Nature 431:873–78
    [Google Scholar]
  181. Wang X, Herr RA, Hansen TH 2012. Ubiquitination of substrates by esterification. Traffic 13:19–24
    [Google Scholar]
  182. Wauer T, Simicek M, Schubert A, Komander D 2015.a Mechanism of phospho-ubiquitin-induced PARKIN activation. Nature 524:370–74
    [Google Scholar]
  183. Wauer T, Swatek KN, Wagstaff JL, Gladkova C, Pruneda JN et al. 2015.b Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis. EMBO J 34:307–25
    [Google Scholar]
  184. Weinberg JS, Drubin DG 2014. Regulation of clathrin-mediated endocytosis by dynamic ubiquitination and deubiquitination. Curr. Biol. 24:951–59
    [Google Scholar]
  185. Welcker M, Orian A, Jin J, Grim JE, Harper JW et al. 2004. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation–dependent c-Myc protein degradation. PNAS 101:9085–90
    [Google Scholar]
  186. Wenzel DM, Lissounov A, Brzovic PS, Klevit RE 2011. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474:105–8
    [Google Scholar]
  187. Werner A, Iwasaki S, McGourty CA, Medina-Ruiz S, Teerikorpi N et al. 2015. Cell-fate determination by ubiquitin-dependent regulation of translation. Nature 525:523–27
    [Google Scholar]
  188. Wertz IE, Newton K, Seshasayee D, Kusam S, Lam C et al. 2015. Phosphorylation and linear ubiquitin direct A20 inhibition of inflammation. Nature 528:370–75
    [Google Scholar]
  189. Wickliffe KE, Lorenz S, Wemmer DE, Kuriyan J, Rape M 2011. The mechanism of linkage-specific ubiquitin chain elongation by a single-subunit E2. Cell 144:769–81
    [Google Scholar]
  190. Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV et al. 2011. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 333:228–33
    [Google Scholar]
  191. Williams C, van den Berg M, Geers E, Distel B 2008. Pex10p functions as an E3 ligase for the Ubc4p-dependent ubiquitination of Pex5p. Biochem. Biophys. Res. Commun. 374:620–24
    [Google Scholar]
  192. Wilson MD, Benlekbir S, Fradet-Turcotte A, Sherker A, Julien JP et al. 2016. The structural basis of modified nucleosome recognition by 53BP1. Nature 536:100–3
    [Google Scholar]
  193. Woelk T, Oldrini B, Maspero E, Confalonieri S, Cavallaro E et al. 2006. Molecular mechanisms of coupled monoubiquitination. Nat. Cell Biol. 8:1246–54
    [Google Scholar]
  194. Wu X, Johansen JV, Helin K 2013. Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation. Mol. Cell 49:1134–46
    [Google Scholar]
  195. Wurzer B, Zaffagnini G, Fracchiolla D, Turco E, Abert C et al. 2015. Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy. eLife 4:e08941
    [Google Scholar]
  196. Xie Y, Kerscher O, Kroetz MB, McConchie HF, Sung P, Hochstrasser M 2007. The yeast Hex3·Slx8 heterodimer is a ubiquitin ligase stimulated by substrate sumoylation. J. Biol. Chem. 282:34176–84
    [Google Scholar]
  197. Xu G, Chapman JR, Brandsma I, Yuan J, Mistrik M et al. 2015. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature 521:541–44
    [Google Scholar]
  198. Xu M, Skaug B, Zeng W, Chen ZJ 2009. A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFα and IL-1β. Mol. Cell 36:302–14
    [Google Scholar]
  199. Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R et al. 2004. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J 23:2116–25
    [Google Scholar]
  200. Yamano K, Youle RJ 2013. PINK1 is degraded through the N-end rule pathway. Autophagy 9:1758–69
    [Google Scholar]
  201. Yan Q, Dutt S, Xu R, Graves K, Juszczynski P et al. 2009. BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Mol. Cell 36:110–20
    [Google Scholar]
  202. Yanagitani K, Juszkiewicz S, Hegde RS 2017. UBE2O is a quality control factor for orphans of multiprotein complexes. Science 357:472–75
    [Google Scholar]
  203. Yang X, Arines FM, Zhang W, Li M 2018. Sorting of a multi-subunit ubiquitin ligase complex in the endolysosome system. eLife 7:e33116
    [Google Scholar]
  204. Yau R, Rape M 2016. The increasing complexity of the ubiquitin code. Nat. Cell Biol. 18:579–86
    [Google Scholar]
  205. Yau RG, Doerner K, Castellanos ER, Haakonsen DL, Werner A et al. 2017. Assembly and function of heterotypic ubiquitin chains in cell-cycle and protein quality control. Cell 171:918–33.e20
    [Google Scholar]
  206. Yoon CH, Lee J, Jongeward GD, Sternberg PW 1995. Similarity of sli-1, a regulator of vulval development in C. elegans, to the mammalian proto-oncogene c-cbl. Science 269:1102–5
    [Google Scholar]
  207. Zelcer N, Hong C, Boyadjian R, Tontonoz P 2009. LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science 325:100–4
    [Google Scholar]
  208. Zhang L, Ding X, Cui J, Xu H, Chen J et al. 2011. Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation. Nature 481:204–8
    [Google Scholar]
  209. Zhang Y, Nicholatos J, Dreier JR, Ricoult SJ, Widenmaier SB et al. 2014. Coordinated regulation of protein synthesis and degradation by mTORC1. Nature 513:440–43
    [Google Scholar]
  210. Zhang ZR, Bonifacino JS, Hegde RS 2013. Deubiquitinases sharpen substrate discrimination during membrane protein degradation from the ER. Cell 154:609–22
    [Google Scholar]
  211. Zhao Y, Brickner JR, Majid MC, Mosammaparast N 2014. Crosstalk between ubiquitin and other post-translational modifications on chromatin during double-strand break repair. Trends Cell Biol 24:426–34
    [Google Scholar]
  212. Zhu L, Jorgensen JR, Li M, Chuang YS, Emr SD 2017. ESCRTs function directly on the lysosome membrane to downregulate ubiquitinated lysosomal membrane proteins. eLife 6:e26403
    [Google Scholar]
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