Receptor downregulation and multivesicular-body sorting

Nature Reviews Molecular Cell Biology

Volumn 3, Issue 12, 2002, Pages 893-905

  Katzmann, David J ^a   Odorizzi, Greg ^b   Emr, Scott D ^c  

^a MAYO CLINIC   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL RECEPTOR; UBIQUITIN;

CANCER; CELL FUNCTION; CELL MEMBRANE TRANSPORT; CLINICAL PATHWAY; COMPLEX FORMATION; ENDOSOME; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MEMBRANE VESICLE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; RECEPTOR DOWN REGULATION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; SPECIES DIFFERENCE;

ANIMALS; CARRIER PROTEINS; CYTOPLASMIC VESICLES; DOWN-REGULATION; ENDOSOMES; EPIDERMAL GROWTH FACTOR; HUMANS; MEMBRANE PROTEINS; MODELS, BIOLOGICAL; PHOSPHOLIPIDS; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; RECEPTORS, CELL SURFACE; RECEPTORS, NOTCH; SACCHAROMYCES CEREVISIAE PROTEINS; SIGNAL TRANSDUCTION; UBIQUITIN; VESICULAR TRANSPORT PROTEINS; YEASTS;

HUMAN IMMUNODEFICIENCY VIRUS;

EID: 0036902646     PISSN: 14710072     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrm973     Document Type: Review

References (118)

1. Gruenberg, J. The endocytic pathway: A mosaic of domains. Nature Rev. Mol. Cell Biol. 2, 721-730 (2001).
2. Mellman, I. Endocytosis and molecular sorting. Annu. Rev. Cell Dev. Biol. 12, 575-625 (1996).
3. Palade, G. E. A small particulate component of the cytoplasm. J. Biophys. Biochem. Cytol. 1, 59-67 (1955).
4. Sotelo, J. R. & Porter, K. R. An electron microscope study of the rat ovum. J. Biophys. Biochem. Cytol. 5, 327-342 (1959).
5. Hirsch, J. G., Fedorko, M. E. & Cohn, Z. A. Vesicle fusion and formation at the surface of pinocytic vacuoles in macrophages. J. Cell Biol. 38, 629-632 (1968).
6. Gorden, P., Carpentier, J. L., Cohen, S. & Orci, L. Epidermal growth factor: Morphological demonstration of binding, internalization, and lysosomal association in human fibroblasts, Proc. Natl. Acad. Sci. USA 75, 5025-5029 (1978).
7. Haigler, H. T., McKanna, J. A. & Cohen, S. Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431. J. Cell Biol. 81, 382-395 (1979). References 6 and 7 followed the delivery of internalized material from the plasma membrane through the MVB pathway to the lysosome, and thereby ascribed a function to the MVBs.
8. Miller, K., Beardmore, J., Kanety, H., Schlessinger, J. & Hopkins, C. R. Localization of the epidermal growth factor (EGF) receptor within the endosome of EGF-stimulated epidermoid carcinoma (A431) cells. J. Cell Biol. 102, 500-509 (1986).
9. Futter, C. E., Pearse, A., Hewlett, L. J. & Hopkins, C. R. Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse diractly with lysosomes. J. Cell Biol. 132, 1011-1023 (1996). This paper showed that EGFRs are delivered to the lysosome through the MVB pathway.
10. Baass, P. C., Di Guglielmo, G. M., Authier, F., Posner, B. I. & Bergeron, J. J. M. Compartmentalized signal transduction by receptor tyrosine kinases. Trends Cell Biol. 5, 465-470 (1995).
11. Di Guglielmo, G. M., Baass, P. C., Ou, W. J., Posner, B. I. & Bergeron, J. J. Compartmentalization of SHC, GRB2 and mSOS, and hyperphosphorylation of Raf-1 by EGF but not insulin in liver parenchyma. EMBO J. 13, 4269-4277 (1994).
12. Grimes, M. L. et al. Endocytosis of activated TrkA: Evidence that nerve growth factor induces formation of signaling endosomes. J. Neurosci. 16, 7950-7964 (1996).
13. Sorkin, A., Eriksson, A., Heldin, C. H., Westermark, B., & Claesson-Welsh. L. Pool of ligand-bound platelet-derived growth factor β-receptors remain activated and tyrosine phosphorylated after internalization. J. Cell Physiol. 156, 373-382 (1993).
14. Wang, Z., Tung, P. S. Moran, M. F. Association of p120 ras GAP with endocytic components and colocalization with epidermal growth factor (EGF) receptor in response to EGF stimulation. Cell Growth Differ. 7,123-133 (1996).
15. Zhang, Y., Moheban, D. B., Conway, B. R., Bhattacharyya, A. & Segal, R. A. Cell surface Trk receptors mediate NGF-induced survival while internalized receptors regulate NGF-induced differentiation. J. Neurosci. 20, 5671-5678 (2000).
16. Ceresa, B. R. & Schmid, S. L. Regulation of signal transduction by endocytosis. Curr. Opin. Cell Biol. 12, 204-210 (2000).
17. Di Fiore, P. P. & Gill, G. N. Endocytosis and mitogenic signaling. Curr. Opin. Cell Biol. 11, 483-488 (1999).
18. Lloyd, T. E. et al. Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell 108, 261-269 (2002).
19. Aroian, R. V., Koga, M., Mendel, J. E., Ohshima, Y. & Sternberg, P W. The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily, Nature 348, 693-699 (1990).
20. Kil, S. J. & Carlin, C. EGF receptor residues leu(679), leu(680) mediate selective sorting of ligand-receptor complexes in early endosomal compartments. J. Cell Physiol. 185, 47-60 (2000).
21. Felder, S. et al. Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body. Cell 61, 623-634 (1990).
22. Sprague, G. F. & Thomer, J. W. in The Molecular and Cellular Biology of the Yeast Saccharomyces Vol. 2 (eds Jones, E. W., Pringle, J. R. & Broach, J. R.) 657-744 (Cold Spring Harbor Laboratory Press, Plainview, New York, 1992).
23. Odorizzi, G., Babst, M. & Emr, S. D. Fab1p Ptdlns(3)P 5-kinase function essential for protein sorting in the multivesicular body. Cell 95, 847-858 (1998).
24. Terrell, J., Shih, S., Dunn, R. & Hicke, L. A function for monoubiquitination in the internalization of a G protein-coupled receptor. Mol. Cell 1, 193-202 (1998).
25. Shih, S. C., Sloper-Mould, K. E. & Hicke, L. Monoubiquitin carries a novel internalization signal that is appended to activated receptors. EMBO J. 19, 187-198 (2000).
26. Dupre, S. & Haguenauer-Tsapis, R. Deubiquitination step in the endocytic pathway of yeast plasma membrane proteins: Crucial role of Doa4p ubiquitin isopeptidase. Mol. Cell Biol. 21, 4482-4494 (2001).
27. Losko, S., Kopp, F., Kranz, A. & Kolling, R. Uptake of the ATP-binding cassette (ABC) transporter Ste6 into the yeast vacuole is blocked in the doa4 mutant. Mol. Biol. Cell 12, 1047-1059 (2001).
28. Springael, J. Y. & Andre, B. Nitrogen-regulated ubiquitination of the Gap1 permease of Saccharomyces cerevisiae. Mol. Biol. Cell 9, 1253-1263 (1998).
29. Helliwell, S. B., Losko, S. & Kaiser, C. A. Components of a ubiquitin ligase complex specify polyubiquitination and intracellular trafficking of the general amino acid permease. J. Cell Biol. 153, 649-662 (2001).
30. Marchese, A. & Benovic, J. L. Agonist-prompted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting. J. Biol. Chem. 276, 45509-45512 (2001).
31. Joazeiro, C. A. et al. The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase, Science 286, 309-312 (1999). This reference, together with references 32, 33 and 34, showed the ubiquitin ligase activity of Cbl, and indicated that failure to ubiquitylate EGFR contributes to the tumongenicity seen in the presence of oncogenic forms of Cbl.
32. Levkowitz, G. et al. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-CbVSli-1. Mol. Cell 4, 1029-1040 (1999).
33. Waterman, H., Levkowitz, G., Alroy, I. & Yarden, Y. The RING finger of c-Cbl mediates desensitization of the epidermal growth factor receptor. J. Biol. Chem. 274, 22151-22154 (1999).
34. Yokouchi, M. et al. Ligand-induced ubiquitination of the epidermal growth factor receptor involves the interaction of the c-Cbl RING finger and UbcH7. J. Biol. Chem. 274, 31707-31712 (1999).
35. Levkowitz, G. et al. c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. Genes Dev. 12, 3663-3674 (1998). This paper showed a role for Cbl in the postinternalization sorting of EGFR.
36. Thien, C. B., Walker, F. & Langdon, W. Y. RING finger mutations that abolish c-Cbl-directed poyubiquitination and downregulation of the EGF receptor are insufficient for cell ceil transformation. Mol. Cell 7, 355-365 (2001).
37. Blake, T. J., Shapiro, M., Morse, H. C. & Langdon, W. Y. The sequences of the human and mouse c-cbl protooncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipperlike motif. Oncogene 6, 653-657 (1991).
38. Chen, L. & Davis, N. G. Ubiquitin-independent entry into the yeast recycling pathway. Traffic 3, 110-123 (2002).
39. Govers, R., ten Broeke, T., van Kerkhof, P., Schwartz, A. L. & Strous, G. J. Identification of a novel ubiquitin conjugation motif, required for ligand-induced internalization of the growth hormone receptor. EMBO J. 18, 28-36 (1999).
40. van Delft, S., Govers, R. Strous, G. J., Verkleij Verklelj, A. J. & van Bergen en Henegouwen, P. M. Epidermal growth factor induces ubiquitination of Eps15. J. Biol. Chem. 272, 14013-14016 (1997).
41. Polo, S et al. A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins Nature 416, 451-455 (2002). This paper reported that the UIM not only binds ubiquitin, but also recruits ubiquitin ligase, which results in the mono-ubiquitination of UIM-containing proteins.
42. Raiborg, C. et al. Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes. Nature Cell Biol. 4, 394-398 (2002).
43. Shenoy, S. K., McDonald, P. H., Kohout, T. A. & Lefkowitz, R. J. Regulation of receptor fate by ubiquitination of activated β2-adrenergic receptor and β-arrestin, Science 294, 1307-1313 (2001).
44. Dunn, R. & Hicke, L. Multiple roles for Rsp5p-dependent ubiquitination at the internalization step of endocytosis. J. Biol. Chem. 278, 25974-25981 (2001).
45. Katzmann, D. J., Babst, M. & Emr, S. D. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106, 145-155 (2001). This paper, together with references 46 and 47, showed that ubiquitin is an endosomal sorting signal, and also identified ESCRT-1 as the machinery that interacts with ubiquitylated MVB cargo.
46. Urbanowski, J. L. & Piper, R. C. Ubiquitin sorts proteins into the intralumenal degradative compartment of the late-endosome/vacuole. Traffic 2, 622-630 (2001).
47. Reggiori, F. & Pelham, H. R. Sorting of proteins into multivesicular bodies: Ubiquitin-dependent and independent targeting. EMBO J. 20, 5176-5186 (2001).
48. Reggiod, F. & Pelham, H. R. A transmembrane ubiquitin ligase required to sort membrane proteins into multivesicular bodies. Nature Cell Biol. 4, 117-123 (2002).
49. Swaminathan, S., Amenk, A. Y. & Hochstrasser, M. The Dca4 deubiquitinating enzyme is required for ubiquitin homeostasis in yeast. Mol. Biol. Cell 10, 2583-2594 (1999).
50. Amerik, A. Y., Nowak, J., Swaminathan, S. & Hochstrasser, M. The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways. Mol. Biol. Cell 11, 3365-3380 (2000). This study identified a role for Doa4 in the de-ubiquitylation of MVB cargoes.
51. Biederer, T., Volkwein, C. & Sommer, T. Role of Cue1p in ubiquitination and degradation at the ER surface. Science 278, 1806-1809 (1997).
52. Hofmann, K. & Bucher, P. The UBA domain: A sequence motif present in multiple enzyme classes of the ubiquitination pathway. Trends Biochem. Sci. 21, 172-173 (1996).
53. Hofmann, R. M. & Pickart, C. M. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96, 645-653 (1999).
54. Hofmann, K. & Falquet, L. A ubliquitin-interacting motif conserved in components of the proteasomal and lysosomal protein degradation systems. Trends Biochem. Sci. 26, 347-350 (2001).
55. Koonin, E. V. & Abagyan, R. A. TSG101 may be the prototype of a class of dominant negative ubiquitin regulators. Nature Genet. 16, 330-331 (1997).
56. Ponting, C. P., Cai, Y. D. & Bork, P. The breast cancer gene product TSG101: A regulator of ubiquitination? J. Mol. Med. 75,467-469 (1997).
57. Conibear, E. & Stevens, T. H. Multiple sorting pathways between the late Golgi and the vacuole in yeast. Biochim. Biophys. Acta 1404, 211-230 (1998).
58. Rieder, S. E., Banta, L. M., Köhrer K., McCaffery, J. M. & Emr, S. D. Multilamellar endosome-like compartment accumulates in the yeast vps28 vacuolar protein sorting mutant. Mol. Biol. Cell 7, 985-999 (1996).
59. Babst, M., Odorizzi, G. Estepa, E. J. & Emr, S. D. Mammalian tumor susceptibility gene 101 (TSG101) and the yeast homologue, Vps23p, both function in late endosomal trafficking. Traffic 1, 248-258 (2000).
60. Garrus, J. E. et al. Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding Cell 107, 55-65 (2001). This paper showed that the class E Vps proteins have a role in HIV-1 budding.
61. Pornillos, O. et al. Structure and functional interactions of the Tag101 UEV domain. EMBO J. 21, 2397-2406 (2002).
62. Li, Y., Kane, T., Tipper, C., Spatrick, P. & Jenness, D. D. Yeast mutants affecting possible quality control of plasma membrane proteins. Mol. Cell. Biol. 19, 3588-3599 (1999).
63. Bishop, N. & Woodman, P. ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking. Mol. Biol. Cell 11, 227-239 (2000).
64. Li, L. & Cohen, S. N. Tsg101: A novel tumor susceptibility gene isolated by controlled homozygous functional knockout of allelic loci in mammalian cells. Cell 85, 319-329 (1996).
65. Shih, S. C. et al. Epsins and Vps27/Hrs contain ubiquitin-binding domains that function in receptor endocytosis and downregulation. Nature Cell Biol. 4, 389-393 (2002).
66. Bilodeau, P. S., Urbanowski, J. L., Winistorfer, S. C. & Piper, R. C. The Vps27p Hse1p complex binds ubiquitin and mediates endosomal protein sorting. Nature Cell Biol. 4, 534-539 (2002).
67. Raiborg, C., Bache, K. G., Mehlum, A., Stang, E. & Stenmark, H. Hrs recruits clathrin to early endosomes. EMBO J. 20, 5008-5021 (2001).
68. Sachse, M., Urbe, S., Oorschot, V., Strous, G. J. & Kumperman, J. Bilayered clathrin coats on endosomal vacuoles are involved in protein sorting toward lysosomes. Mol. Biol. Cell 13, 1313-1328 (2002).
69. Nielsen, M. S. et al. The sortilln cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein. EMBO J. 20, 2180-2190 (2001).
70. Puertollano, R., Aguilar, R. C., Gorshkova, I., Crouch, R. J. & Bonifacino, J. S. Sorting of mannose 6-phosphate receptors mediated by the GGAs Science 292, 1712-1716 (2001).
71. Misra, S., Puertollano, R., Kato, Y., Bonifacino, J. S. & Hurley, J. H. Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains. Nature 415, 933-937 (2002).
72. Shiba, T. et al. Structural basis for recognition of acidic-cluster dlleucine sequence by GGA1. Nature 415, 937-941 (2002).
73. Babst. M., Katzman, D. J., Snyder, W. B., Wendland, B. & Emr. S. D. Endosome-associated complex, ESCRT-II, directs recruitment of machinery required for protein sorting into multivesicular bodies. Dev. Cell 3,283-289 (2002).
74. Davis, N. G., Horecka, J. L. & Sprague, G. F. Jr Cis-and trans-acting functions required for endocytosis of the yeast pheromone receptors. J. Cell Biol. 122, 53-65 (1993).
75. Nathwehr, S. F. Bryant, N. J. & Stevens, T. H. The newly identified yeast GRD genes are required for retention of late-Golgi membrane proteins. Mol. Cell Biol. 16, 2700-2707 (1996)
76. Babst, M., Katzman, D. J., Estepa, E. J., Meerloo, T. & Emr, S. D. ESCRT-III: An endosome associated hetero-oligomeric protein complex required for MVB sorting. Dev. Cell 3, 271-282 (2002). References 73 and 76 further characterize the ESCRT complexes.
77. Ashrafi, K., Farazi, T. A. & Gordon, J. I. A role for Saccharomyces cerevisiae fatty acid activation protein 4 in regulating protein N-myristoylation during entry into stationary phase. J. Biol. Chem. 273, 25864-25874 (1998).
78. Babst, M., Wendland, B., Estepa, E. J. & Emr, S. D. The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function. EMBO J. 17, 2982-2993 (1998). This work showed that Vps4 encodes an AAA-ATPase that is required for the release of MVB sorting components.
79. Babst, M., Sato, T. K., Banta, L. M. & Emr, S. D. Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4p. EMBO J. 16, 1820-1831 (1997).
80. Kobayashi, T. et al. A lipid associated with the antiphospholipid syndrome regulates endosome structure and function. Nature 392, 193-197 (1998).
81. Kobayashi, T. et al. Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport. Nature Cell Biol. 1, 113-118 (1999).
82. Odorizzi, G., Babst, M. & Emr, S. D. Phosphoinositide signaling and the regulation of membrane trafficking in yeast Trends Biochem. Sci. 25, 229-235 (2000).
83. Sato, T. K., Overduin, M. & Emr, S. D. Location, location, location: Membrane targeting directed by PX domains. Science 294, 1881-1885 (2001).
84. Tsukazaki, T., Chiang, T. A., Davison, A. F., Attisano, L. & Wrana, J. L. SARA, a FYVE domain protein that recruits Smad2 to the TGFβ receptor, Cell 95, 779-791 (1998).
85. Gillooly, D. J. et al. Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells. EMBO J. 19, 4577-4588 (2000).
86. Wurmser, A. E. & Emr, S. D. Phosphoinositide signaling and turnover: Ptdlns(3)P, a regulator of membrane traffic, is transported to the vacuole and degraded by a process that requires lumenal vacuolar hydrolase activities. EMBO J. 17, 4930-4942 (1998).
87. Schu, P. V. et al. Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science 260, 88-91 (1993). References 85, 86 and 87 showed a role for Ptdlns(3)P in MVB formation and that Ptdlns(3)P is present on lumenal vesicles.
88. Fernandez-Borja, M. et al. Multivesicular body morphogenesis requires phosphatidyl-inositol 3-kinase activity. Curr. Biol. 9, 55-58 (1999).
89. Futter, C. E., Collinson, L. M., Backer, J. M. & Hopkins, C. R. Human VPS34 is required for internal vesicle formation within multivesicular endosomes. J. Cell Biol. 155, 1251-1264 (2001).
90. Gary, J. D., Wurmser, A. E., Bonangelino, C. J., Weisman, L. S. & Emr, S. D. Fab1p is essential for Ptdlns(3)P 5-kinase activity and the maintenance of vacuolar size and membrane homeostasis. J. Cell Biol. 143, 65-79 (1998).
91. Artavanis-Tsakonas, S., Rand, M. D. & Lake, R. J. Notch signaling: Cell fate control and signal integration in development. Science 284, 770-776 (1999).
92. Berset, T., Hoier, E. F., Battu, G., Canevascini, S. & Hajnal, A. Notch inhibition of RAS signaling through MAP kinase phosphatase LIP-1 during C. elegans vulval development. Science 291, 1055-1058 (2001).
93. Schroeter, E. H., Kisslinger, J. A. & Kopan, R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393, 382-386 (1998).
94. Struhl, G. & Adachi, A. Nuclear access and action of notch in vivo. Cell 93, 649-660 (1998).
95. Deblandre, G. A., Lai, E. C. & Kintner, C. Xenopus neuralized is a ubiquitin ligase that interacts with XDelta1 and regulates Notch signaling. Dev. Cell 1, 795-806 (2001).
96. Lai, E. C., Deblandre, G. A., Kintner, C. & Rubin, G. M. Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of delta. Dev. Cell 1, 783-794 (2001).
97. Pavlopoulos, E. et al. Neuralized encodes a peripheral membrane protein involved in delta signaling and endocytosis. Dev. Cell 1, 807-816 (2001). References 95, 96, and 97 showed a role for ubiquitin ligase in developmental signalling.
98. Kleijmeer, M. et al. Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells. J. Cell Biol. 155, 53-64 (2001).
99. Zitvogel, L. et al. Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell-derived exosomes. Nature Med. 4, 594-600 (1998).
100. Ott, D. E., Coren, L. V., Chertova, E. N., Gagliardi, T. D. & Schubert, U. Ubiquitination of HIV-1 and MuLV Gag. Virology 278, 111-121 (2000).
101. Schubert, U. et al. Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2. Proc. Natl. Acad. Sci. USA 97, 13057-13062 (2000).
102. Strack, B., Calistri, A. Accola, M. A., Palu, G. & Gottlinger, H. G. A role for ubiquitin ligase recruitment in retrovirus release. Proc. Natl. Acad. Sci. USA 97, 13063-13068 (2000). Papers 100, 101 and 102 highlighted a role for ubiquitin in retroviral budding.
103. Martin-Serrano, J., Zang, T. & Bieniasz, P. D. HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nature Med. 7, 1313-1319 (2001).
104. Bays, N. W., Gardner, R. G., Seelig, L. P., Joazeiro, C. A. & Hampton, R. Y. Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nature Cell Biol. 3, 24-29 (2001).
105. Bonifacino, J. S. & Weissman, A. M. Ubiquitin and the control of protein fate in the secretory and endocytic pathways. Annu. Rev. Cell Dev. Biol. 14, 19-57 (1998).
106. Tsai, B., Ye, Y. & Rapoport, T. A. Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nature Rev. Mol. Cell Biol. 3, 246-255 (2002).
107. Chau, V. et al. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243, 1576-1583 (1989).
108. Thrower, J. S., Hoffman, L., Rechsteiner, M. & Pickart, C. M. Recognition of the polyubiquitin proteolytic signal. EMBO J. 19, 94-102 (2000).
109. Cowles, C. R., Snyder, W. B., Burd, C. G. & Emr, S. D. An alternative Golgi to vacuole delivery pathway in yeast: Identification of a sorting determinant and required transport component. EMBO J. 16, 2769-2782 (1997).
110. Galan, J. M., Moreau, V., Andre, B., Volland, C. & Haguenauer-Tsapis, R. Ubiquitination mediated by the Npi1p/Rsp5p ubiquitin-protein ligase is required for endocytosis of the yeast uracil permease. J. Biol. Chem. 271, 10946-10952 (1996).
111. Egner, R. & Kuchler, K. The yeast multidrug transporter Pdr5 of the plasma membrane is ubiquitinated prior to endocytosis and degradation in the vacuole. FEBS Lett. 378, 177-181 (1996).
112. Kolling, R. & Hollenberg, C. The ABC-transporter Ste6 accumulates in the plasma membrane in a ubiquitinated form in endocytosis mutants. EMBO J. 13, 3261-3271 (1994).
113. Beck, T., Schmidt, A. & Hall, M. N. Starvation induces vacuolar targeting and degradation of the tryptophan permease in yeast. J. Cell Biol. 146, 1227-1238 (1999).
114. Strous, G. J., van Kerkhof, P., Govers, R., Ciechanover, A. & Schwartz, A. L. The ubiquitin conjugation system is required for ligand-induced endocytosis and degradation of the growth hormone receptor. EMBO J. 15, 3806-3812 (1996).
115. Rocca, A., Lamaze, C., Subtil, A. & Dautry-Varsat, A. Involvement of the ubiquitin/proteasome system in sorting of the interleukin 2 receptor β chain to late endocytic compartments. Mol. Biol. Cell 12, 1293-1301 (2001).
116. Fujita, Y. et al. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nature Cell Biol. 4, 222-231 (2002).
117. + channel (ENaC) by ubiquitination. EMBO J. 16, 6325-6336 (1997).
118. Gottschalk, S., Waheed, A., Schmidt, B., Laidler, P. & von Figura, K. Sequential processing of lysosomal acid phosphatase by a cytoplasmic thiol proteinase and a lysosomal aspartyl proteinase. EMBO J. 8, 3215-3219 (1989).