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Regulation of Endocytic Trafficking and Signalling by Deubiquitylating Enzymes

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Vesicle Trafficking in Cancer

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Abstract

As the major route by which activated Receptor Tyrosine Kinases are degraded, the endolysosomal pathway may be seen as a tumour suppressor pathway. The appendage of ubiquitin chains to activated receptors provides a sorting signal for sorting into multivesicular bodies which go on to fuse directly with lysosomes. Deubiquitylating (DUB) activities, such as the endosome-localised AMSH and USP8, can favour recycling of receptors by reducing this active sorting into MVBs. These enzymes have an overlapping set of binding partners at the endosome, which include both early- and late-acting components of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery. The exact interplay between these enzymes is still under debate. The consequences of depletion can be complex and need to be interpreted with care. Generically endosomal DUBs can influence receptor trafficking by direct deubiquitylation of receptors or associated proteins, by stabilisation of sorting factors or by contributing to free ubiquitin homeostasis by recycling ubiquitin once a MVB cargo molecule has been committed to degradation. We propose that a single endosomal DUB may carry out multiple functions depending on the suite of interactions being employed. Recent studies have provided further examples of DUBs which may associate with endosomes in a transient manner to influence the sorting of RTKs but also other types of receptors, such as GPCRs and various channels.

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Bibliography

  1. Clague MJ, Urbe S (2010) Ubiquitin: same molecule, different degradation pathways. Cell 143:682–685

    Article  PubMed  CAS  Google Scholar 

  2. Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479

    Article  PubMed  CAS  Google Scholar 

  3. Henne WM, Buchkovich NJ, Emr SD (2011) The ESCRT Pathway. Dev Cell 21:77–91

    Article  PubMed  CAS  Google Scholar 

  4. Futter CE, Pearse A, Hewlett LJ, Hopkins CR (1996) Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse directly with lysosomes. J Cell Biol 132:1011–1023

    Article  PubMed  CAS  Google Scholar 

  5. Mosesson Y, Mills GB, Yarden Y (2008) Derailed endocytosis: an emerging feature of cancer. Nat Rev Cancer 8:835–850

    Article  PubMed  CAS  Google Scholar 

  6. Peschard P, Park M (2003) Escape from Cbl-mediated downregulation: a recurrent theme for oncogenic deregulation of receptor tyrosine kinases. Cancer Cell 3:519–523

    Article  PubMed  CAS  Google Scholar 

  7. Abella JV, Peschard P, Naujokas MA, Lin T, Saucier C, Urbe S, Park M (2005) Met/Hepatocyte growth factor receptor ubiquitination suppresses transformation and is required for Hrs phosphorylation. Mol Cell Biol 25:9632–9645

    Article  PubMed  CAS  Google Scholar 

  8. Thompson BJ, Mathieu J, Sung HH, Loeser E, Rorth P, Cohen SM (2005) Tumor suppressor properties of the ESCRT-II complex component Vps25 in Drosophila. Dev Cell 9:711–720

    Article  PubMed  CAS  Google Scholar 

  9. Sorkin A (1998) Endocytosis and intracellular sorting of receptor tyrosine kinases. Front Biosci 3:729–738

    Google Scholar 

  10. Sigismund S, Confalonieri S, Ciliberto A, Polo S, Scita G, Di Fiore PP (2012) Endocytosis and signaling: cell logistics shape the eukaryotic cell plan. Physiol Rev 92:273–366

    Article  PubMed  CAS  Google Scholar 

  11. Grabbe C, Husnjak K, Dikic I (2011) The spatial and temporal organization of ubiquitin networks. Nat Rev Mol Cell Biol 12:295–307

    Article  PubMed  CAS  Google Scholar 

  12. Woelk T, Oldrini B, Maspero E, Confalonieri S, Cavallaro E, Di Fiore PP, Polo S (2006) Molecular mechanisms of coupled monoubiquitination. Nat Cell Biol 8:1246–1254

    Article  PubMed  CAS  Google Scholar 

  13. Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A (2006) Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell 21:737–748

    Article  PubMed  CAS  Google Scholar 

  14. Vina-Vilaseca A, Sorkin A (2010) Lysine 63-linked polyubiquitination of the dopamine transporter requires WW3 and WW4 domains of Nedd4-2 and UBE2D ubiquitin-conjugating enzymes. J Biol Chem 285:7645–7656

    Article  PubMed  CAS  Google Scholar 

  15. Reggiori F, Pelham HR (2001) Sorting of proteins into multivesicular bodies: ubiquitin-­dependent and -independent targeting. EMBO J 20:5176–5186

    Article  PubMed  CAS  Google Scholar 

  16. Sigismund S, Woelk T, Puri C, Maspero E, Tacchetti C, Transidico P, Di Fiore PP, Polo S (2005) Clathrin-independent endocytosis of ubiquitinated cargos. Proc Natl Acad Sci U S A 102:2760–2765

    Article  PubMed  CAS  Google Scholar 

  17. Haglund K, Dikic I (2012) The role of ubiquitylation in receptor endocytosis and endosomal sorting. J Cell Sci 125:265–275

    Article  PubMed  CAS  Google Scholar 

  18. Lauwers E, Erpapazoglou Z, Haguenauer-Tsapis R, Andre B (2010) The ubiquitin code of yeast permease trafficking. Trends Cell Biol 20:196–204

    Article  PubMed  CAS  Google Scholar 

  19. Behrends C, Harper JW (2011) Constructing and decoding unconventional ubiquitin chains. Nat Struct Mol Biol 18:520–528

    Article  PubMed  CAS  Google Scholar 

  20. Li JG, Haines DS, Liu-Chen LY (2008) Agonist-promoted Lys63-linked polyubiquitination of the human kappa-opiod receptor is involved in receptor down-regulation. Mol Pharmacol 73:1319–1330

    Article  PubMed  CAS  Google Scholar 

  21. Duncan LM, Piper S, Dodd RB, Saville MK, Sanderson CM, Luzio JP, Lehner PJ (2006) Lysine-63-linked ubiquitination is required for endolysosomal degradation of class I molecules. EMBO J 25:1635–1645

    Article  PubMed  CAS  Google Scholar 

  22. Finley D (2009) Recognition and processing of ubiquitin-protein conjugates by the proteasome. Ann Rev Biochem 78:477–513

    Article  PubMed  CAS  Google Scholar 

  23. Clague MJ, Urbe S (2006) Endocytosis: the DUB version. Trends Cell Biol 16:551–559

    Article  PubMed  CAS  Google Scholar 

  24. Kimura Y, Yashiroda H, Kudo T, Koitabashi S, Murata S, Kakizuka A, Tanaka K (2009) An inhibitor of a deubiquitinating enzyme regulates ubiquitin homeostasis. Cell 137:549–559

    Article  PubMed  CAS  Google Scholar 

  25. Carter S, Urbe S, Clague MJ (2004) The met receptor degradation pathway: requirement for Lys48-linked polyubiquitin independent of proteasome activity. J Biol Chem 279:52835–52839

    Article  PubMed  CAS  Google Scholar 

  26. Nijman SM, Luna-Vargas MP, Velds A, Brummelkamp TR, Dirac AM, Sixma TK, Bernards R (2005) A genomic and functional inventory of deubiquitinating enzymes. Cell 123:773–786

    Article  PubMed  CAS  Google Scholar 

  27. Komander D, Clague MJ, Urbe S (2009) Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol 10:550–563

    Article  PubMed  CAS  Google Scholar 

  28. Ventii KH, Wilkinson KD (2008) Protein partners of deubiquitinating enzymes. Biochem J 414:161–175

    Article  PubMed  CAS  Google Scholar 

  29. Kouranti I, McLean JR, Feoktistova A, Liang P, Johnson AE, Roberts-Galbraith RH, Gould KL (2010) A global census of fission yeast deubiquitinating enzyme localization and interaction networks reveals distinct compartmentalization profiles and overlapping functions in endocytosis and polarity. PLoS Biol 8(9)

    Google Scholar 

  30. Amerik AY, Li SJ, Hochstrasser M (2000) Analysis of the deubiquitinating enzymes of the yeast Saccharomyces cerevisiae. Biol Chem 381:981–992

    Article  PubMed  CAS  Google Scholar 

  31. Amerik AY, Hochstrasser M (2004) Mechanism and function of deubiquitinating enzymes. Biochim Biophys Acta 1695:189–207

    Article  PubMed  CAS  Google Scholar 

  32. Shimanuki M, Saka Y, Yanagida M, Toda T (1995) A novel essential fission yeast gene pad1+ positively regulates pap1(+)-dependent transcription and is implicated in the maintenance of chromosome structure. J Cell Sci 108(Pt 2):569–579

    PubMed  CAS  Google Scholar 

  33. Strous GJ, Van Kerhhof P, Govers R, Ciechanover A, Schwartz AL (1996) The ubiquitin conjugation system is required for ligand-induced endocytosis and degradation of the growth-­hormone receptor. EMBO J 15:3806–3812

    PubMed  CAS  Google Scholar 

  34. Cenciarelli C, Hou D, Hsu KC, Rellahan BL, Wiest DL, Smith HT, Fried VA, Weissman AM (1992) Activation-induced ubiquitination of the T cell antigen receptor. Science 257:795–797

    Article  PubMed  CAS  Google Scholar 

  35. Hicke L, Riezman H (1996) Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell 84:277–287

    Article  PubMed  CAS  Google Scholar 

  36. Galan JM, Moreau V, Andre B, Volland C, Haguenauer-Tsapis R (1996) Ubiquitination mediated by the Npi1p/Rsp5p ubiquitin-protein ligase is required for endocytosis of the yeast uracil permease. J Biol Chem 271:10946–10952

    Article  PubMed  CAS  Google Scholar 

  37. Odorizzi G, Katzmann DJ, Babst M, Audhya A, Emr SD (2003) Bro1 is an endosome-­associated protein that functions in the MVB pathway in Saccharomyces cerevisiae. J Cell Sci 116:1893–1903

    Article  PubMed  CAS  Google Scholar 

  38. Nikko E, Marini AM, Andre B (2003) Permease recycling and ubiquitination status reveal a particular role for Bro1 in the multivesicular body pathway. J Biol Chem 278:50732–50743

    Article  PubMed  CAS  Google Scholar 

  39. Luhtala N, Odorizzi G (2004) Bro1 coordinates deubiquitination in the multivesicular body pathway by recruiting Doa4 to endosomes. J Cell Biol 166:717–729

    Article  PubMed  CAS  Google Scholar 

  40. Richter C, West M, Odorizzi G (2007) Dual mechanisms specify Doa4-mediated deubiquitination at multivesicular bodies. EMBO J 26:2454–2464

    Article  PubMed  CAS  Google Scholar 

  41. Papa FR, Hochstrasser M (1993) The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene. Nature 366:313–319

    Article  PubMed  CAS  Google Scholar 

  42. Galan JM, Haguenauer-Tsapis R (1997) Ubiquitin lys63 is involved in ubiquitination of a yeast plasma membrane protein. EMBO J 16:5847–5854

    Article  PubMed  CAS  Google Scholar 

  43. Springael JY, Galan JM, Haguenauer-Tsapis R, Andre B (1999) NH4+−induced down-­regulation of the Saccharomyces cerevisiae Gap1p permease involves its ubiquitination with lysine-63-linked chains. J Cell Sci 112(Pt 9):1375–1383

    PubMed  CAS  Google Scholar 

  44. Loayza D, Michaelis S (1998) Role for the ubiquitin-proteasome system in the vacuolar degradation of Ste6p, the a-factor transporter in Saccharomyces cerevisiae. Mol Cell Biol 18:779–789

    PubMed  CAS  Google Scholar 

  45. Lucero P, Lagunas R (1997) Catabolite inactivation of the yeast maltose transporter requires ubiquitin-ligase npi1/rsp5 and ubiquitin-hydrolase npi2/doa4. FEMS Microbiol Lett 147:273–277

    Article  PubMed  CAS  Google Scholar 

  46. Amerik AY, Nowak J, Swaminathan S, Hochstrasser M (2000) The DoA4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways. Mol Biol Cell 11:3365–3380

    PubMed  CAS  Google Scholar 

  47. Dupre S, Haguenauer-Tsapis R (2001) Deubiquitination step in the endocytic pathway of yeast plasma membrane proteins: crucial role of Doa4p ubiquitin isopeptidase. Mol Cell Biol 21:4482–4494

    Article  PubMed  CAS  Google Scholar 

  48. Nikko E, Andre B (2007) Evidence for a direct role of the Doa4 deubiquitinating enzyme in protein sorting into the MVB pathway. Traffic 8:566–581

    Article  PubMed  CAS  Google Scholar 

  49. Kee Y, Lyon N, Huibregtse JM (2005) The Rsp5 ubiquitin ligase is coupled to and antagonized by the Ubp2 deubiquitinating enzyme. EMBO J 24:2414–2424

    Article  PubMed  CAS  Google Scholar 

  50. Kee Y, Munoz W, Lyon N, Huibregtse JM (2006) The deubiquitinating enzyme Ubp2 modulates Rsp5-dependent Lys63-linked polyubiquitin conjugates in Saccharomyces cerevisiae. J Biol Chem 281:36724–36731

    Article  PubMed  CAS  Google Scholar 

  51. Ren J, Kee Y, Huibregtse JM, Piper RC (2007) Hse1, a component of the yeast Hrs-STAM ubiquitin-sorting complex, associates with ubiquitin peptidases and a ligase to control sorting efficiency into multivesicular bodies. Mol Biol Cell 18:324–335

    Article  PubMed  CAS  Google Scholar 

  52. Lam MH, Urban-Grimal D, Bugnicourt A, Greenblatt JF, Haguenauer-Tsapis R, Emili A (2009) Interaction of the deubiquitinating enzyme Ubp2 and the e3 ligase Rsp5 is required for transporter/receptor sorting in the multivesicular body pathway. PLoS One 4:e4259

    Article  PubMed  CAS  Google Scholar 

  53. Onishi M, Nakamura Y, Koga T, Takegawa K, Fukui Y (2003) Isolation of suppressor mutants of phosphatidylinositol 3-phosphate 5-kinase deficient cells in Schizosaccharomyces pombe. Biosci Biotechnol Biochem 67:1772–1779

    Article  PubMed  CAS  Google Scholar 

  54. de Lartigue J, Polson H, Feldman M, Shokat K, Tooze SA, Urbe S, Clague MJ (2009) PIKfyve regulation of endosome-linked pathways. Traffic 10:883–893

    Article  PubMed  CAS  Google Scholar 

  55. Iwaki T, Onishi M, Ikeuchi M, Kita A, Sugiura R, Giga-Hama Y, Fukui Y, Takegawa K (2007) Essential roles of class E Vps proteins for sorting into multivesicular bodies in Schizosaccharomyces pombe. Microbiology 153:2753–2764

    Article  PubMed  CAS  Google Scholar 

  56. Urbe S, Liu H, Hayes SD, Heride C, Rigden DJ, Clague MJ (2012) Systematic survey of deubiquitinase localisation identifies USP21 as a regulator of centrosome and microtubule associated functions. Mol Biol Cell 23(6):1095–1103

    Article  PubMed  CAS  Google Scholar 

  57. Row PE, Prior IA, McCullough J, Clague MJ, Urbe S (2006) The ubiquitin isopeptidase UBPY regulates endosomal ubiquitin dynamics and is essential for receptor down-regulation. J Biol Chem 281:12618–12624

    Article  PubMed  CAS  Google Scholar 

  58. Tanaka N, Kaneko K, Asao H, Kasai H, Endo Y, Fujita T, Takeshita T, Sugamura K (1999) Possible involvement of a novel STAM-associated molecule “AMSH” in intracellular signal transduction mediated by cytokines. J Biol Chem 274:19129–19135

    Article  PubMed  CAS  Google Scholar 

  59. Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (2001) Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads. EMBO J 20:4132–4142

    Article  PubMed  CAS  Google Scholar 

  60. McCullough J, Clague MJ, Urbe S (2004) AMSH is an endosome-associated ubiquitin isopeptidase. J Cell Biol 166:487–492

    Article  PubMed  CAS  Google Scholar 

  61. Kato M, Miyazawa K, Kitamura N (2000) A de-ubiquitinating enzyme UBPY interacts with the SH3 domain of Hrs binding protein via a novel binding motif Px(V/I)(D/N)RxxKP. J Biol Chem 275:37481–37487

    Article  PubMed  CAS  Google Scholar 

  62. Hurley JH, Yang D (2008) MIT domainia. Dev Cell 14:6–8

    Article  PubMed  CAS  Google Scholar 

  63. Sachse M, Urbé S, Oorschot V, Strous GJ, Klumperman J (2002) Bilayered clathrin coats on endosomal vacuoles are involved in protein sorting toward lysosomes. Mol Biol Cell 13:1313–1328

    Article  PubMed  CAS  Google Scholar 

  64. Clague MJ (2002) Membrane transport: a coat for ubiquitin. Curr Biol 12:R529–R531

    Article  PubMed  CAS  Google Scholar 

  65. Raiborg C, Wesche J, Malerod L, Stenmark H (2006) Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains. J Cell Sci 119:2414–2424

    Article  PubMed  CAS  Google Scholar 

  66. Nakamura M, Tanaka N, Kitamura N, Komada M (2006) Clathrin anchors deubiquitinating enzymes, AMSH and AMSH-like protein, on early endosomes. Genes Cells 11:593–606

    Article  PubMed  CAS  Google Scholar 

  67. Kyuuma M, Kikuchi K, Kojima K, Sugawara Y, Sato M, Mano N, Goto J, Takeshita T, Yamamoto A, Sugamura K et al (2007) AMSH, an ESCRT-III associated enzyme, deubiquitinates cargo on MVB/late endosomes. Cell Struct Funct 31:159–172

    Article  PubMed  Google Scholar 

  68. Ma YM, Boucrot E, Villen J, Affar el B, Gygi SP, Gottlinger HG, Kirchhausen T (2007) Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation. J Biol Chem 282:9805–9812

    Article  PubMed  CAS  Google Scholar 

  69. McCullough J, Row PE, Lorenzo O, Doherty M, Beynon R, Clague MJ, Urbe S (2006) Activation of the endosome-associated ubiquitin isopeptidase AMSH by STAM, a component of the multivesicular body-sorting machinery. Curr Biol 16:160–165

    Article  PubMed  CAS  Google Scholar 

  70. Hurley JH, Stenmark H (2011) Molecular mechanisms of ubiquitin-dependent membrane traffic. Annu Rev Biophys 40:119–142

    Article  PubMed  CAS  Google Scholar 

  71. Tsang HT, Connell JW, Brown SE, Thompson A, Reid E, Sanderson CM (2006) A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex. Genomics 88(3):333–346

    Article  PubMed  CAS  Google Scholar 

  72. Agromayor M, Martin-Serrano J (2006) Interaction of AMSH with ESCRT-III and deubiquitination of endosomal cargo. J Biol Chem 281:1374–1387

    Article  CAS  Google Scholar 

  73. Row PE, Liu H, Hayes S, Welchman R, Charalabous P, Hofmann K, Clague MJ, Sanderson CM, Urbe S (2007) The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation. J Biol Chem 282:30929–30937

    Article  PubMed  CAS  Google Scholar 

  74. Solomons J, Sabin C, Poudevigne E, Usami Y, Hulsik DL, Macheboeuf P, Hartlieb B, Gottlinger H, Weissenhorn W (2011) Structural Basis for ESCRT-III CHMP3 Recruitment of AMSH. Structure 19:1149–1159

    Article  PubMed  CAS  Google Scholar 

  75. Komander D, Reyes-Turcu F, Licchesi JDF, Odenwaelder P, Wilkinson KD, Barford D (2009) Molecular discrimination of structurally equivalent Lys63-linked and linear polyubiquitin chains. EMBO Rep 10:466–473

    Article  PubMed  CAS  Google Scholar 

  76. Sato Y, Yoshikawa A, Yamagata A, Mimura H, Yamashita M, Ookata K, Nureki O, Iwai K, Komada M, Fukai S (2008) Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains. Nature 455:358–362

    Article  PubMed  CAS  Google Scholar 

  77. Lauwers E, Jacob C, Andre B (2009) K63-linked ubiquitin chains as a specific signal for protein sorting into the multivesicular body pathway. J Cell Biol 185:493–502

    Article  PubMed  CAS  Google Scholar 

  78. Bowers K, Piper SC, Edeling MA, Gray SR, Owen DJ, Lehner PJ, Luzio JP (2006) Degradation of endocytosed epidermal growth factor and virally ubiquitinated major histocompatibility complex class I is independent of mammalian ESCRTII. J Biol Chem 281:5094–5105

    Article  PubMed  CAS  Google Scholar 

  79. Pareja F, Ferraro DA, Rubin C, Cohen-Dvashi H, Zhang F, Aulmann S, Ben-Chetrit N, Pines G, Navon R, Crosetto N et al (2012) Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. Oncogene 31(43):4599–4608

    Article  PubMed  CAS  Google Scholar 

  80. Sierra MI, Wright MH, Nash PD (2010) AMSH interacts with ESCRT-0 to regulate the stability and trafficking of CXCR4. J Biol Chem 285:13990–14004

    Article  PubMed  CAS  Google Scholar 

  81. Reyes-Ibarra AP, Garcia-Regalado A, Ramirez-Rangel I, Esparza-Silva AL, Valadez-Sanchez M, Vazquez-Prado J, Reyes-Cruz G (2007) Calcium-sensing receptor endocytosis links extracellular calcium signaling to parathyroid hormone-related peptide secretion via a Rab11a-­dependent and AMSH-sensitive mechanism. Mol Endocrinol 21:1394–1407

    Article  PubMed  CAS  Google Scholar 

  82. Hasdemir B, Murphy JE, Cottrell GS, Bunnett NW (2009) Endosomal deubiquitinating enzymes control ubiquitination and down-regulation of protease-activated receptor 2. J Biol Chem 284:28453–28466

    Article  PubMed  CAS  Google Scholar 

  83. Naviglio S, Mattecucci C, Matoskova B, Nagase T, Nomura N, Di Fiore PP, Draetta GF (1998) UBPY: a growth-regulated human ubiquitin isopeptidase. EMBO J 17:3241–3250

    Article  PubMed  CAS  Google Scholar 

  84. Niendorf S, Oksche A, Kisser A, Lohler J, Prinz M, Schorle H, Feller S, Lewitzky M, Horak I, Knobeloch KP (2007) Essential role of ubiquitin-specific protease 8 for receptor tyrosine kinase stability and endocytic trafficking in vivo. Mol Cell Biol 27:5029–5039

    Article  PubMed  CAS  Google Scholar 

  85. Mizuno E, Iura T, Mukai A, Yoshimori T, Kitamura N, Komada M (2005) Regulation of epidermal growth factor receptor down-regulation by ubpy-mediated deubiquitination at endosomes. Mol Biol Cell 16:5163–5174

    Article  PubMed  CAS  Google Scholar 

  86. Avvakumov GV, Walker JR, Xue S, Finerty PJ Jr, Mackenzie F, Newman EM, Dhe-Paganon S (2006) Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8). J Biol Chem 281:38061–38070

    Article  PubMed  CAS  Google Scholar 

  87. Wu X, Yen L, Irwin L, Sweeney C, Carraway KL 3rd (2004) Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating enzyme USP8. Mol Cell Biol 24:7748–7757

    Article  PubMed  CAS  Google Scholar 

  88. Faesen AC, Luna-Vargas MPA, Geurink PP, Clerici M, Merkx R, van Dijk WJ, Hameed DS, El Oualid F, Ovaa H, Sixma TK (2011) The differential modulation of USP activity by internal regulatory domains, interactors and eight ubiquitin chain types. Chem Biol 18:1550–1561

    Article  PubMed  CAS  Google Scholar 

  89. Mizuno E, Kobayashi K, Yamamoto A, Kitamura N, Komada M (2006) A deubiquitinating enzyme UBPY regulates the level of protein ubiquitination on endosomes. Traffic 7:1017–10131

    Article  PubMed  CAS  Google Scholar 

  90. Brocker C, Kuhlee A, Gatsogiannis C, Balderhaar HJ, Honscher C, Engelbrecht-Vandre S, Ungermann C, Raunser S (2011) Molecular architecture of the multisubunit homotypic fusion and vacuole protein sorting (HOPS) tethering complex. Proc Natl Acad Sci U S A 109:1991–1996

    Article  CAS  Google Scholar 

  91. Mukai A, Yamamoto-Hino M, Awano W, Watanabe W, Komada M, Goto S (2010) Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. EMBO J 29:2114–2125

    Article  PubMed  CAS  Google Scholar 

  92. Xia R, Jia H, Fan J, Liu Y, Jia J (2012) USP8 promotes smoothened signaling by preventing its ubiquitination and changing its subcellular localization. PLoS Biol 10:e1001238

    Article  PubMed  CAS  Google Scholar 

  93. Li S, Chen Y, Shi Q, Yue T, Wang B, Jiang J (2012) Hedgehog-regulated ubiquitination controls smoothened trafficking and cell surface expression in Drosophila. PLoS Biol 10:e1001239

    Article  PubMed  CAS  Google Scholar 

  94. Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M (2011) Global quantification of mammalian gene expression control. Nature 473:337–342

    Article  PubMed  CAS  Google Scholar 

  95. Raiborg C, Gronvold Bache K, Mehlum A, Stang E, Stenmark H (2001) Hrs recruits clathrin to early endosomes. EMBO J 20:5008–5021

    Article  PubMed  CAS  Google Scholar 

  96. Raiborg C, Bache KG, Gillooly DJ, Madshus IH, Stang E, Stenmark H (2002) Hrs sorts ubiquitinated proteins into clathrin -coated microdomains of early endosomes. Nat Cell Biol 4:394–398

    Article  PubMed  CAS  Google Scholar 

  97. Wollert T, Hurley JH (2010) Molecular mechanism of multivesicular body biogenesis by ESCRT complexes. Nature 464:864–869

    Article  PubMed  CAS  Google Scholar 

  98. Scott A, Gaspar J, Stuchell-Brereton MD, Alam SL, Skalicky JJ, Sundquist WI (2005) Structure and ESCRT-III protein interactions of the MIT domain of human VPS4A. Proc Natl Acad Sci U S A 102:13813–13818

    Article  PubMed  CAS  Google Scholar 

  99. Shenoy SK, Modi AS, Shukla AK, Xiao K, Berthouze M, Ahn S, Wilkinson KD, Miller WE, Lefkowitz RJ (2009) Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2. Proc Natl Acad Sci U S A 106:6650–6655

    Article  PubMed  CAS  Google Scholar 

  100. Berthouze M, Venkataramanan V, Li Y, Shenoy SK (2009) The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. EMBO J 28:1684–1696

    Article  PubMed  CAS  Google Scholar 

  101. Fakitsas P, Adam G, Daidie D, van Bemmelen MX, Fouladkou F, Patrignani A, Wagner U, Warth R, Camargo SM, Staub O et al (2007) Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation. J Am Soc Nephrol 18:1084–1092

    Article  PubMed  CAS  Google Scholar 

  102. Boulkroun S, Ruffieux-Daidie D, Vitagliano JJ, Poirot O, Charles RP, Lagnaz D, Firsov D, Kellenberger S, Staub O (2008) Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3. Am J Physiol Renal Physiol 295:F889–F900

    Article  PubMed  CAS  Google Scholar 

  103. Bomberger JM, Barnaby RL, Stanton BA (2010) The deubiquitinating enzyme USP10 regulates the endocytic recycling of CFTR in airway epithelial cells. Channels (Austin) 4:150–154

    Article  CAS  Google Scholar 

  104. Bomberger JM, Barnaby RL, Stanton BA (2009) The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of cystic fibrosis transmembrane conductance regulator in airway epithelial cells. J Biol Chem 284:18778–18789

    Article  PubMed  CAS  Google Scholar 

  105. Gorbea C, Pratt G, Ustrell V, Bell R, Sahasrabudhe S, Hughes RE, Rechsteiner M (2010) A protein interaction network for ECM29 links the 26S proteasome to molecular motors and endosomal components. J Biol Chem 285:31616–31633

    Article  PubMed  CAS  Google Scholar 

  106. Hammond DE, Urbe S, Vande Woude GF, Clague MJ (2001) Down-regulation of MET, the receptor for hepatocyte growth factor. Oncogene 20:2761–2770

    Article  PubMed  CAS  Google Scholar 

  107. Alwan HA, van Zoelen EJ, van Leeuwen JE (2003) Ligand-induced lysosomal epidermal growth factor receptor (EGFR) degradation is preceded by proteasome-dependent EGFR de-­ubiquitination. J Biol Chem 278:35781–35790

    Article  PubMed  CAS  Google Scholar 

  108. Geetha T, Wooten MW (2008) TrkA receptor endolysosomal degradation is both ubiquitin and proteasome dependent. Traffic 9:1146–1156

    Article  PubMed  CAS  Google Scholar 

  109. Colland F (2010) The therapeutic potential of deubiquitinating enzyme inhibitors. Biochem Soc Trans 38:137–143

    Article  PubMed  CAS  Google Scholar 

  110. Fry WH, Simion C, Sweeney C, Carraway KL 3rd (2011) Quantity control of the ErbB3 receptor tyrosine kinase at the endoplasmic reticulum. Mol Cell Biol 31:3009–3018

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Cellular and Molecular Physiology, Institute of Translational Medicine, The University of Liverpool, Liverpool, L69 3BX, UK

    Han Liu, Sylvie Urbé & Michael J. Clague

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  1. Han Liu
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  2. Sylvie Urbé
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  3. Michael J. Clague
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Correspondence to Michael J. Clague .

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  1. Department of Biological Regulation, Candiotty Bldg, Hertzel St 1, Rehovot, 76100, Israel

    Yosef Yarden

  2. , Department of Biological Regulation, Weizmann Institute of Science, Hertzl Street 1, Rehovot, 76100, Israel

    Gabi Tarcic

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Liu, H., Urbé, S., Clague, M.J. (2013). Regulation of Endocytic Trafficking and Signalling by Deubiquitylating Enzymes. In: Yarden, Y., Tarcic, G. (eds) Vesicle Trafficking in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6528-7_12

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