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PMID: 24384571 Published · epublish English Journal Article Review

Ubiquitin-dependent sorting in endocytosis.

Cold Spring Harbor perspectives in biology ·Vol. 6 ·No. 1 ·2014-01-01

Piper RC, Dikic I, Lukacs GL

Abstract

When ubiquitin (Ub) is attached to membrane proteins on the plasma membrane, it directs them through a series of sorting steps that culminate in their delivery to the lumen of the lysosome where they undergo complete proteolysis. Ubiquitin is recognized by a series of complexes that operate at a number of vesicle transport steps. Ubiquitin serves as a sorting signal for internalization at the plasma membrane and is the major signal for incorporation into intraluminal vesicles of multivesicular late endosomes. The sorting machineries that catalyze these steps can bind Ub via a variety of Ub-binding domains. At the same time, many of these complexes are themselves ubiquitinated, thus providing a plethora of potential mechanisms to regulate their activity. Here we provide an overview of how membrane proteins are selected for ubiquitination and deubiquitination within the endocytic pathway and how that ubiquitin signal is interpreted by endocytic sorting machineries.

MeSH Terms
Binding Sites Cell Membrane/metabolism Endocytosis/physiology Protein Transport Proteolysis Ubiquitin/physiology
Chemicals
Ubiquitin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Piper Robert C
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242.
Dikic Ivan
Lukacs Gergely L
References (183)
183 references, click to expand
  1. AMSH interacts with ESCRT-0 to regulate the stability and trafficking of CXCR4.
    J Biol Chem. 2010 Apr 30;285(18):13990-4004 PMID: 20159979
  2. Internal amino acids promote Gap1 permease ubiquitylation via TORC1/Npr1/14-3-3-dependent control of the Bul arrestin-like adaptors.
    Mol Cell Biol. 2012 Nov;32(22):4510-22 PMID: 22966204
  3. The arrestin domain-containing 3 protein regulates body mass and energy expenditure.
    Cell Metab. 2011 Nov 2;14(5):671-83 PMID: 21982743
  4. Rabex-5 ubiquitin ligase activity restricts Ras signaling to establish pathway homeostasis in Drosophila.
    Curr Biol. 2010 Aug 10;20(15):1378-82 PMID: 20655224
  5. Spatiotemporal regulation of the ubiquitinated cargo-binding activity of Rabex-5 in the endocytic pathway.
    J Biol Chem. 2012 Nov 23;287(48):40586-97 PMID: 23048039
  6. Transport activity-dependent intracellular sorting of the yeast general amino acid permease.
    Mol Biol Cell. 2011 Jun 1;22(11):1919-29 PMID: 21471002
  7. Conformational selection and induced fit mechanism underlie specificity in noncovalent interactions with ubiquitin.
    Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19346-51 PMID: 19887638
  8. Monoubiquitin carries a novel internalization signal that is appended to activated receptors.
    EMBO J. 2000 Jan 17;19(2):187-98 PMID: 10637223
  9. NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway.
    Nat Struct Mol Biol. 2012 Apr 01;19(5):511-6, S1 PMID: 22466964
  10. The Hrs/STAM complex in the downregulation of receptor tyrosine kinases.
    J Biochem. 2005 Jan;137(1):1-8 PMID: 15713877
  11. Molecular mechanisms of the membrane sculpting ESCRT pathway.
    Cold Spring Harb Perspect Biol. 2013 Sep 01;5(9): PMID: 24003212
  12. A dual role for K63-linked ubiquitin chains in multivesicular body biogenesis and cargo sorting.
    Mol Biol Cell. 2012 Jun;23(11):2170-83 PMID: 22493318
  13. Isoform-specific monoubiquitination, endocytosis, and degradation of alternatively spliced ErbB4 isoforms.
    Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4162-7 PMID: 18334649
  14. Protein quality control at the plasma membrane.
    Curr Opin Cell Biol. 2011 Aug;23(4):483-91 PMID: 21571517
  15. Routing misfolded proteins through the multivesicular body (MVB) pathway protects against proteotoxicity.
    J Biol Chem. 2011 Aug 19;286(33):29376-29387 PMID: 21708947
  16. An inhibitor of a deubiquitinating enzyme regulates ubiquitin homeostasis.
    Cell. 2009 May 1;137(3):549-59 PMID: 19410548
  17. Ubiquitin chain conformation regulates recognition and activity of interacting proteins.
    Nature. 2012 Dec 13;492(7428):266-70 PMID: 23201676
  18. Non-canonical ubiquitylation: mechanisms and consequences.
    Int J Biochem Cell Biol. 2013 Aug;45(8):1833-42 PMID: 23732108
  19. Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation.
    Nat Cell Biol. 2003 May;5(5):461-6 PMID: 12717448
  20. Disorder targets misorder in nuclear quality control degradation: a disordered ubiquitin ligase directly recognizes its misfolded substrates.
    Mol Cell. 2011 Jan 7;41(1):93-106 PMID: 21211726
  21. Ubiquitin-specific protease 2-45 (Usp2-45) binds to epithelial Na+ channel (ENaC)-ubiquitylating enzyme Nedd4-2.
    Am J Physiol Renal Physiol. 2011 Jul;301(1):F189-96 PMID: 21478478
  22. Cytoplasmic tail phosphorylation of the alpha-factor receptor is required for its ubiquitination and internalization.
    J Cell Biol. 1998 Apr 20;141(2):349-58 PMID: 9548714
  23. Ubiquitin dynamics in complexes reveal molecular recognition mechanisms beyond induced fit and conformational selection.
    PLoS Comput Biol. 2012;8(10):e1002704 PMID: 23055911
  24. Doa4 function in ILV budding is restricted through its interaction with the Vps20 subunit of ESCRT-III.
    J Cell Sci. 2013 Apr 15;126(Pt 8):1881-90 PMID: 23444383
  25. Ubiquitination by the membrane-associated RING-CH-8 (MARCH-8) ligase controls steady-state cell surface expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor 1.
    J Biol Chem. 2013 Mar 1;288(9):6617-28 PMID: 23300075
  26. Regulation of ubiquitin-binding proteins by monoubiquitination.
    Nat Cell Biol. 2006 Feb;8(2):163-9 PMID: 16429130
  27. Arrestin-2 interacts with the ubiquitin-protein isopeptide ligase atrophin-interacting protein 4 and mediates endosomal sorting of the chemokine receptor CXCR4.
    J Biol Chem. 2007 Dec 21;282(51):36971-9 PMID: 17947233
  28. Solution structure of the ESCRT-I and -II supercomplex: implications for membrane budding and scission.
    Structure. 2012 May 9;20(5):874-86 PMID: 22579254
  29. ALIX is a Lys63-specific polyubiquitin binding protein that functions in retrovirus budding.
    Dev Cell. 2012 Dec 11;23(6):1247-54 PMID: 23201121
  30. Peripheral protein quality control removes unfolded CFTR from the plasma membrane.
    Science. 2010 Aug 13;329(5993):805-10 PMID: 20595578
  31. Bsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins.
    EMBO J. 2004 Mar 24;23(6):1279-88 PMID: 14988731
  32. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4.
    Dev Cell. 2003 Nov;5(5):709-22 PMID: 14602072
  33. The ubiquitin-specific protease USP2a prevents endocytosis-mediated EGFR degradation.
    Oncogene. 2013 Mar 28;32(13):1660-9 PMID: 22710717
  34. Goliath family E3 ligases regulate the recycling endosome pathway via VAMP3 ubiquitylation.
    EMBO J. 2013 Feb 20;32(4):524-37 PMID: 23353890
  35. Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination.
    Cell. 2013 Feb 28;152(5):1051-64 PMID: 23452853
  36. A role for the ESCRT system in cell division in archaea.
    Science. 2008 Dec 12;322(5908):1710-3 PMID: 19008417
  37. UBPY-mediated epidermal growth factor receptor (EGFR) de-ubiquitination promotes EGFR degradation.
    J Biol Chem. 2007 Jan 19;282(3):1658-69 PMID: 17121848
  38. A molecular switch on an arrestin-like protein relays glucose signaling to transporter endocytosis.
    J Cell Biol. 2012 Jan 23;196(2):247-59 PMID: 22249293
  39. Plasma membrane deformation by circular arrays of ESCRT-III protein filaments.
    J Cell Biol. 2008 Jan 28;180(2):389-402 PMID: 18209100
  40. Conjugation to Nedd8 instigates ubiquitylation and down-regulation of activated receptor tyrosine kinases.
    J Biol Chem. 2006 Aug 4;281(31):21640-21651 PMID: 16735510
  41. Lysine 63-linked polyubiquitination is required for EGF receptor degradation.
    Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15722-7 PMID: 24019463
  42. Dynamics of endosomal sorting complex required for transport (ESCRT) machinery during cytokinesis and its role in abscission.
    Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4846-51 PMID: 21383202
  43. Cell signaling by receptor tyrosine kinases.
    Cell. 2010 Jun 25;141(7):1117-34 PMID: 20602996
  44. Nedd4-2 catalyzes ubiquitination and degradation of cell surface ENaC.
    J Biol Chem. 2007 Jul 13;282(28):20207-12 PMID: 17502380
  45. Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.
    Mol Cell. 2005 Nov 23;20(4):525-38 PMID: 16307917
  46. Mammalian α arrestins link activated seven transmembrane receptors to Nedd4 family e3 ubiquitin ligases and interact with β arrestins.
    PLoS One. 2012;7(12):e50557 PMID: 23236378
  47. Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1.
    Mol Biol Cell. 2013 Feb;24(3):308-18 PMID: 23242996
  48. Chaperone functions of the E3 ubiquitin ligase CHIP.
    J Biol Chem. 2007 Aug 3;282(31):22267-77 PMID: 17545168
  49. The ubiquitin code of yeast permease trafficking.
    Trends Cell Biol. 2010 Apr;20(4):196-204 PMID: 20138522
  50. Ubiquitin conjugation to Gag is essential for ESCRT-mediated HIV-1 budding.
    Retrovirology. 2013 Jul 29;10:79 PMID: 23895345
  51. Role of ubiquitylation and USP8-dependent deubiquitylation in the endocytosis and lysosomal targeting of plasma membrane KCa3.1.
    FASEB J. 2011 Nov;25(11):3938-48 PMID: 21828287
  52. Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes.
    Nat Cell Biol. 2002 May;4(5):394-8 PMID: 11988743
  53. Bro1 coordinates deubiquitination in the multivesicular body pathway by recruiting Doa4 to endosomes.
    J Cell Biol. 2004 Aug 30;166(5):717-29 PMID: 15326198
  54. Plasticity of polyubiquitin recognition as lysosomal targeting signals by the endosomal sorting machinery.
    Mol Biol Cell. 2007 Oct;18(10):3952-65 PMID: 17686993
  55. Differential requirements of mammalian ESCRTs in multivesicular body formation, virus budding and cell division.
    FEBS J. 2012 Apr;279(8):1399-406 PMID: 22340600
  56. A concentric circle model of multivesicular body cargo sorting.
    EMBO Rep. 2007 Jul;8(7):644-50 PMID: 17603537
  57. TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor.
    Cell. 2011 Nov 23;147(5):1104-17 PMID: 22118465
  58. The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways.
    Mol Biol Cell. 2000 Oct;11(10):3365-80 PMID: 11029042
  59. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain.
    Mol Cell. 2006 Mar 17;21(6):737-48 PMID: 16543144
  60. Clathrin-independent endocytosis of ubiquitinated cargos.
    Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2760-5 PMID: 15701692
  61. Membrane-associated RING-CH (MARCH) 8 mediates the ubiquitination and lysosomal degradation of the transferrin receptor.
    J Cell Sci. 2013 Jul 1;126(Pt 13):2798-809 PMID: 23606747
  62. Atypical ubiquitylation - the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages.
    Nat Rev Mol Cell Biol. 2012 Jul 23;13(8):508-23 PMID: 22820888
  63. How ubiquitin functions with ESCRTs.
    Traffic. 2011 Oct;12(10):1306-17 PMID: 21722280
  64. Regulation of endocytic sorting by ESCRT-DUB-mediated deubiquitination.
    Cell Biochem Biophys. 2011 Jun;60(1-2):39-46 PMID: 21448666
  65. Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes.
    J Cell Biol. 2003 Aug 4;162(3):435-42 PMID: 12900395
  66. Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body.
    Dev Cell. 2002 Aug;3(2):283-9 PMID: 12194858
  67. The role of ubiquitylation in receptor endocytosis and endosomal sorting.
    J Cell Sci. 2012 Jan 15;125(Pt 2):265-75 PMID: 22357968
  68. Sna3 is an Rsp5 adaptor protein that relies on ubiquitination for its MVB sorting.
    Traffic. 2012 Apr;13(4):586-98 PMID: 22212814
  69. Regulation of endocytic clathrin dynamics by cargo ubiquitination.
    Dev Cell. 2012 Sep 11;23(3):519-32 PMID: 22940114
  70. c-Cbl-mediated neddylation antagonizes ubiquitination and degradation of the TGF-β type II receptor.
    Mol Cell. 2013 Feb 7;49(3):499-510 PMID: 23290524
  71. A conserved late endosome-targeting signal required for Doa4 deubiquitylating enzyme function.
    J Cell Biol. 2006 Dec 4;175(5):825-35 PMID: 17145966
  72. Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains.
    Nature. 2008 Sep 18;455(7211):358-62 PMID: 18758443
  73. βTrCP interacts with the ubiquitin-dependent endocytosis motif of the GH receptor in an unconventional manner.
    Biochem J. 2013 Jul 15;453(2):291-301 PMID: 23607312
  74. Membrane scission by the ESCRT-III complex.
    Nature. 2009 Mar 12;458(7235):172-7 PMID: 19234443
  75. Ubiquitin-mediated targeting of a mutant plasma membrane ATPase, Pma1-7, to the endosomal/vacuolar system in yeast.
    Mol Biol Cell. 2004 May;15(5):2401-9 PMID: 15020711
  76. Monoubiquitination of EEA1 regulates endosome fusion and trafficking.
    Cell Biosci. 2013 May 23;3(1):24 PMID: 23701900
  77. Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain.
    Nat Struct Mol Biol. 2009 Dec;16(12):1328-30 PMID: 19935683
  78. Dictyostelium Tom1 participates to an ancestral ESCRT-0 complex.
    Traffic. 2009 Feb;10(2):161-71 PMID: 19054384
  79. Cargo ubiquitination is essential for multivesicular body intralumenal vesicle formation.
    EMBO Rep. 2012 Apr;13(4):331-8 PMID: 22370727
  80. Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2.
    J Biol Chem. 2004 Jul 9;279(28):28930-5 PMID: 15123669
  81. Helical structures of ESCRT-III are disassembled by VPS4.
    Science. 2008 Sep 5;321(5894):1354-7 PMID: 18687924
  82. Extracellular vesicles: exosomes, microvesicles, and friends.
    J Cell Biol. 2013 Feb 18;200(4):373-83 PMID: 23420871
  83. UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting.
    Curr Biol. 2011 Jul 26;21(14):1245-50 PMID: 21757351
  84. Membrane-elasticity model of Coatless vesicle budding induced by ESCRT complexes.
    PLoS Comput Biol. 2012;8(10):e1002736 PMID: 23093927
  85. Cbl-dependent ubiquitination is required for progression of EGF receptors into clathrin-coated pits.
    Mol Biol Cell. 2004 Aug;15(8):3591-604 PMID: 15194809
  86. Down-regulating destruction: phosphorylation regulates the E3 ubiquitin ligase Nedd4-2.
    Sci Signal. 2009 Jul 14;2(79):pe41 PMID: 19602703
  87. Membrane budding and scission by the ESCRT machinery: it's all in the neck.
    Nat Rev Mol Cell Biol. 2010 Aug;11(8):556-66 PMID: 20588296
  88. Following Ariadne's thread: a new perspective on RBR ubiquitin ligases.
    BMC Biol. 2012 Mar 15;10:24 PMID: 22420831
  89. A unique cell division machinery in the Archaea.
    Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18942-6 PMID: 18987308
  90. Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB.
    Curr Biol. 2013 Mar 18;23(6):453-61 PMID: 23477725
  91. A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K-Akt signalling.
    Nat Cell Biol. 2006 Aug;8(8):834-42 PMID: 16862145
  92. Competitive binding of UBPY and ubiquitin to the STAM2 SH3 domain revealed by NMR.
    FEBS Lett. 2012 Sep 21;586(19):3379-84 PMID: 22841719
  93. The trafficking and regulation of membrane receptors by the RING-CH ubiquitin E3 ligases.
    Exp Cell Res. 2009 May 15;315(9):1593-600 PMID: 19013150
  94. Dynamics of ESCRT protein recruitment during retroviral assembly.
    Nat Cell Biol. 2011 Apr;13(4):394-401 PMID: 21394083
  95. The ART-Rsp5 ubiquitin ligase network comprises a plasma membrane quality control system that protects yeast cells from proteotoxic stress.
    Elife. 2013 Apr 16;2:e00459 PMID: 23599894
  96. E3 ubiquitin ligases in ErbB receptor quantity control.
    Semin Cell Dev Biol. 2010 Dec;21(9):936-43 PMID: 20868762
  97. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation.
    Cell. 2009 Mar 20;136(6):1098-109 PMID: 19303852
  98. The HECT domain ligase itch ubiquitinates endophilin and localizes to the trans-Golgi network and endosomal system.
    J Biol Chem. 2004 Mar 19;279(12):11471-9 PMID: 14684745
  99. Feedback regulation of Ras signaling by Rabex-5-mediated ubiquitination.
    Curr Biol. 2010 Aug 10;20(15):1372-7 PMID: 20655225
  100. Yeast mutants affecting possible quality control of plasma membrane proteins.
    Mol Cell Biol. 1999 May;19(5):3588-99 PMID: 10207082
  101. The yeast vps class E mutants: the beginning of the molecular genetic analysis of multivesicular body biogenesis.
    Mol Biol Cell. 2010 Dec;21(23):4057-60 PMID: 21115849
  102. Ubiquitin ligase activity of c-Cbl guides the epidermal growth factor receptor into clathrin-coated pits by two distinct modes of Eps15 recruitment.
    J Biol Chem. 2004 Dec 31;279(53):55465-73 PMID: 15465819
  103. The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain.
    Structure. 2012 Mar 7;20(3):414-28 PMID: 22405001
  104. Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80.
    EMBO J. 2009 Aug 19;28(16):2461-8 PMID: 19536136
  105. The ubiquitin system, an immense realm.
    Annu Rev Biochem. 2012;81:167-76 PMID: 22663079
  106. Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane.
    Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11857-62 PMID: 23818590
  107. The yeast Alix homolog Bro1 functions as a ubiquitin receptor for protein sorting into multivesicular endosomes.
    Dev Cell. 2013 Jun 10;25(5):520-33 PMID: 23726974
  108. Quality control for unfolded proteins at the plasma membrane.
    J Cell Biol. 2010 Nov 1;191(3):553-70 PMID: 20974815
  109. The endosomal sorting complex ESCRT-II mediates the assembly and architecture of ESCRT-III helices.
    Cell. 2012 Oct 12;151(2):356-71 PMID: 23063125
  110. Ubiquitination of alpha 5 beta 1 integrin controls fibroblast migration through lysosomal degradation of fibronectin-integrin complexes.
    Dev Cell. 2010 Jul 20;19(1):148-59 PMID: 20643357
  111. Evidence for cooperative and domain-specific binding of the signal transducing adaptor molecule 2 (STAM2) to Lys63-linked diubiquitin.
    J Biol Chem. 2012 May 25;287(22):18687-99 PMID: 22493438
  112. What has the study of the K3 and K5 viral ubiquitin E3 ligases taught us about ubiquitin-mediated receptor regulation?
    Viruses. 2011 Feb;3(2):118-31 PMID: 22049306
  113. A single ubiquitin is sufficient for cargo protein entry into MVBs in the absence of ESCRT ubiquitination.
    J Cell Biol. 2011 Jan 24;192(2):229-42 PMID: 21242292
  114. Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments.
    Science. 2011 Mar 25;331(6024):1616-20 PMID: 21310966
  115. Intracellular trafficking of interleukin-1 receptor I requires Tollip.
    Curr Biol. 2006 Nov 21;16(22):2265-70 PMID: 17113392
  116. The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization.
    EMBO J. 2009 Jun 17;28(12):1684-96 PMID: 19424180
  117. Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface.
    Cell. 2008 Nov 14;135(4):714-25 PMID: 18976803
  118. ESCRT-0 assembles as a heterotetrameric complex on membranes and binds multiple ubiquitinylated cargoes simultaneously.
    J Biol Chem. 2011 Mar 18;286(11):9636-45 PMID: 21193406
  119. Protein quality control: U-box-containing E3 ubiquitin ligases join the fold.
    Trends Biochem Sci. 2002 Jul;27(7):368-75 PMID: 12114026
  120. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1.
    Mol Cell. 1999 Dec;4(6):1029-40 PMID: 10635327
  121. SCF(TrCP) acts in endosomal sorting of the GH receptor.
    Exp Cell Res. 2011 Apr 15;317(7):1071-82 PMID: 21195069
  122. RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis.
    Nat Rev Cancer. 2011 Aug 24;11(9):629-43 PMID: 21863050
  123. Ubiquitin-interacting motifs of Epsin are involved in the regulation of insulin-dependent endocytosis.
    J Biochem. 2005 Mar;137(3):355-64 PMID: 15809337
  124. Cbl-mediated ubiquitination of alpha5 integrin subunit mediates fibronectin-dependent osteoblast detachment and apoptosis induced by FGFR2 activation.
    J Cell Sci. 2005 Mar 15;118(Pt 6):1223-32 PMID: 15728256
  125. Molecular basis of oligoubiquitin-dependent internalization of membrane proteins in Mammalian cells.
    Traffic. 2006 Mar;7(3):282-97 PMID: 16497223
  126. E3 ubiquitin ligases for MHC molecules.
    Curr Opin Immunol. 2009 Feb;21(1):78-83 PMID: 19203867
  127. Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution.
    Science. 2008 Jun 13;320(5882):1471-5 PMID: 18556554
  128. The epsin protein family: coordinators of endocytosis and signaling.
    Biomol Concepts. 2012 Apr;3(2):117-126 PMID: 22942912
  129. The function of yeast epsin and Ede1 ubiquitin-binding domains during receptor internalization.
    Traffic. 2010 Jan;11(1):151-60 PMID: 19903324
  130. Ubiquitin is required for sorting to the vacuole of the yeast general amino acid permease, Gap1.
    J Biol Chem. 2001 Nov 23;276(47):43949-57 PMID: 11500494
  131. EGF receptor ubiquitination is not necessary for its internalization.
    Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16904-9 PMID: 17940017
  132. Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to mediate ubiquitination of the beta2-adrenergic receptor.
    EMBO Rep. 2010 Aug;11(8):605-11 PMID: 20559325
  133. Governance of endocytic trafficking and signaling by reversible ubiquitylation.
    Dev Cell. 2012 Sep 11;23(3):457-67 PMID: 22975321
  134. The running of the Buls: control of permease trafficking by α-arrestins Bul1 and Bul2.
    Mol Cell Biol. 2012 Nov;32(22):4506-9 PMID: 23028041
  135. ESCRT ubiquitin-binding domains function cooperatively during MVB cargo sorting.
    J Cell Biol. 2009 Apr 20;185(2):213-24 PMID: 19380877
  136. Molecular mechanisms of coupled monoubiquitination.
    Nat Cell Biol. 2006 Nov;8(11):1246-54 PMID: 17013377
  137. Dual mechanisms specify Doa4-mediated deubiquitination at multivesicular bodies.
    EMBO J. 2007 May 16;26(10):2454-64 PMID: 17446860
  138. MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound β(2)-adrenergic receptors.
    J Cell Biol. 2012 Nov 26;199(5):817-30 PMID: 23166351
  139. The Bro1-related protein HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis.
    Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6308-13 PMID: 18434552
  140. In silico elucidation of the recognition dynamics of ubiquitin.
    PLoS Comput Biol. 2011 Apr;7(4):e1002035 PMID: 21533067
  141. Phosphatidylinositol 4-kinase IIα function at endosomes is regulated by the ubiquitin ligase Itch.
    EMBO Rep. 2012 Dec;13(12):1087-94 PMID: 23146885
  142. Tollip, an intracellular trafficking protein, is a novel modulator of the transforming growth factor-β signaling pathway.
    J Biol Chem. 2012 Nov 16;287(47):39653-63 PMID: 23027871
  143. Site-specific ubiquitination exposes a linear motif to promote interferon-alpha receptor endocytosis.
    J Cell Biol. 2007 Dec 3;179(5):935-50 PMID: 18056411
  144. Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors.
    Nature. 2002 Mar 14;416(6877):183-7 PMID: 11894095
  145. Endosome maturation.
    EMBO J. 2011 Aug 31;30(17):3481-500 PMID: 21878991
  146. The Rab5 guanine nucleotide exchange factor Rabex-5 binds ubiquitin (Ub) and functions as a Ub ligase through an atypical Ub-interacting motif and a zinc finger domain.
    J Biol Chem. 2006 Mar 10;281(10):6874-83 PMID: 16407276
  147. AMSH is an endosome-associated ubiquitin isopeptidase.
    J Cell Biol. 2004 Aug 16;166(4):487-92 PMID: 15314065
  148. Structural requirements for recognition of major histocompatibility complex class II by membrane-associated RING-CH (MARCH) protein E3 ligases.
    J Biol Chem. 2012 Aug 17;287(34):28779-89 PMID: 22761441
  149. Interactions of GGA3 with the ubiquitin sorting machinery.
    Nat Cell Biol. 2004 Mar;6(3):244-51 PMID: 15039775
  150. Modularity of the Hrd1 ERAD complex underlies its diverse client range.
    J Cell Biol. 2010 Mar 8;188(5):707-16 PMID: 20212318
  151. Ubiquitin-specific peptidase 8 (USP8) regulates endosomal trafficking of the epithelial Na+ channel.
    J Biol Chem. 2013 Feb 22;288(8):5389-97 PMID: 23297398
  152. Epsin 1 is a polyubiquitin-selective clathrin-associated sorting protein.
    Traffic. 2006 Mar;7(3):262-81 PMID: 16497222
  153. The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation.
    J Biol Chem. 2007 Oct 19;282(42):30929-37 PMID: 17711858
  154. MARCH ubiquitin ligases alter the itinerary of clathrin-independent cargo from recycling to degradation.
    Mol Biol Cell. 2011 Sep;22(17):3218-30 PMID: 21757542
  155. The intertransmembrane region of Kaposi's sarcoma-associated herpesvirus modulator of immune recognition 2 contributes to B7-2 downregulation.
    J Virol. 2012 May;86(9):5288-96 PMID: 22379101
  156. A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins.
    Nature. 2002 Mar 28;416(6879):451-5 PMID: 11919637
  157. Versatile role of the yeast ubiquitin ligase Rsp5p in intracellular trafficking.
    Biochem Soc Trans. 2008 Oct;36(Pt 5):791-6 PMID: 18793138
  158. Components of a ubiquitin ligase complex specify polyubiquitination and intracellular trafficking of the general amino acid permease.
    J Cell Biol. 2001 May 14;153(4):649-62 PMID: 11352928
  159. Regulation of epidermal growth factor receptor ubiquitination and trafficking by the USP8·STAM complex.
    J Biol Chem. 2010 Nov 5;285(45):34909-21 PMID: 20736164
  160. VHS domains of ESCRT-0 cooperate in high-avidity binding to polyubiquitinated cargo.
    EMBO J. 2010 Mar 17;29(6):1045-54 PMID: 20150893
  161. Ubiquitin signals protein trafficking via interaction with a novel ubiquitin binding domain in the membrane fusion regulator, Vps9p.
    Curr Biol. 2003 Feb 4;13(3):258-62 PMID: 12573224
  162. Structural studies of phosphoinositide 3-kinase-dependent traffic to multivesicular bodies.
    Biochem Soc Symp. 2007;(74):47-57 PMID: 17233579
  163. LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor.
    Science. 2009 Jul 3;325(5936):100-4 PMID: 19520913
  164. ARRDC3 suppresses breast cancer progression by negatively regulating integrin beta4.
    Oncogene. 2010 Sep 9;29(36):5032-47 PMID: 20603614
  165. Quality control and substrate-dependent downregulation of the nutrient transporter Fur4.
    Traffic. 2013 Apr;14(4):412-27 PMID: 23305501
  166. Specific recognition of linear ubiquitin chains by the Npl4 zinc finger (NZF) domain of the HOIL-1L subunit of the linear ubiquitin chain assembly complex.
    Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20520-5 PMID: 22139374
  167. Vps9p CUE domain ubiquitin binding is required for efficient endocytic protein traffic.
    J Biol Chem. 2003 May 30;278(22):19826-33 PMID: 12654912
  168. Physiological functions of the HECT family of ubiquitin ligases.
    Nat Rev Mol Cell Biol. 2009 Jun;10(6):398-409 PMID: 19436320
  169. Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions.
    Annu Rev Biochem. 2012;81:291-322 PMID: 22482907
  170. GGA proteins bind ubiquitin to facilitate sorting at the trans-Golgi network.
    Nat Cell Biol. 2004 Mar;6(3):252-9 PMID: 15039776
  171. A new side to ubiquitin.
    Trends Biochem Sci. 2006 Oct;31(10):541-4 PMID: 16901703
  172. Both K63 and K48 ubiquitin linkages signal lysosomal degradation of the LDL receptor.
    J Lipid Res. 2013 May;54(5):1410-20 PMID: 23419260
  173. Ndfip1-deficient mice have impaired DMT1 regulation and iron homeostasis.
    Blood. 2011 Jan 13;117(2):638-46 PMID: 20959604
  174. Monoubiquitylation of GGA3 by hVPS18 regulates its ubiquitin-binding ability.
    Biochem Biophys Res Commun. 2006 Nov 10;350(1):82-90 PMID: 16996030
  175. Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin.
    Science. 2001 Nov 9;294(5545):1307-13 PMID: 11588219
  176. MVB vesicle formation: ESCRT-dependent, ESCRT-independent and everything in between.
    Curr Opin Cell Biol. 2011 Aug;23(4):452-7 PMID: 21570275
  177. Degradation of endocytosed epidermal growth factor and virally ubiquitinated major histocompatibility complex class I is independent of mammalian ESCRTII.
    J Biol Chem. 2006 Feb 24;281(8):5094-105 PMID: 16371348
  178. Ubiquitin binding and conjugation regulate the recruitment of Rabex-5 to early endosomes.
    EMBO J. 2008 Oct 8;27(19):2484-94 PMID: 18772883
  179. Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes.
    Mol Biol Cell. 2005 Nov;16(11):5163-74 PMID: 16120644
  180. Ubiquitin binds to and regulates a subset of SH3 domains.
    Mol Cell. 2007 Jan 26;25(2):273-84 PMID: 17244534
  181. Ubiquitination and degradation of CFTR by the E3 ubiquitin ligase MARCH2 through its association with adaptor proteins CAL and STX6.
    PLoS One. 2013 Jun 20;8(6):e68001 PMID: 23818989
  182. A chimeric pre-ubiquitinated EGF receptor is constitutively endocytosed in a clathrin-dependent, but kinase-independent manner.
    Traffic. 2011 Apr;12(4):507-20 PMID: 21226813
  183. Lysine 63-linked polyubiquitination of the dopamine transporter requires WW3 and WW4 domains of Nedd4-2 and UBE2D ubiquitin-conjugating enzymes.
    J Biol Chem. 2010 Mar 5;285(10):7645-56 PMID: 20051513
Article Info
Journal
Cold Spring Harbor perspectives in biology
Abbr.
Cold Spring Harb Perspect Biol
ISSN
1943-0264
DOI
10.1101/cshperspect.a016808
Published
2014-01-01
Epub
2014-00-01
Language
English
Region
United States
NLM ID
101513680
PMCID
PMC3941215
Subset
IM
Grants
NIGMS NIH HHS · R01 GM058202 · United States
External Links
PubMed source DOI: 10.1101/cshperspect.a016808 PMC Full Text View journal details
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