Ubiquitin-dependent proteolysis: Its role in human diseases and the design of therapeutic strategies

Molecular Genetics and Metabolism

Volumn 77, Issue 1-2, 2002, Pages 44-56

  Sakamoto, Kathleen M ^a,b  

^a Oncology and Gwynne Hazen Cherry Memorial Laboratories   (United States)

^b CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Human disease; Proteolysis; Therapeutics; Ubiquitin; Ubiquitin ligase

Indexed keywords

LIGASE; PROTEASOME; PROTEIN TYROSINE KINASE INHIBITOR; UBIQUITIN; BETA TRANSDUCIN REPEAT CONTAINING PROTEIN; BTRC PROTEIN, HUMAN; CBL PROTEIN; CBL PROTEIN, HUMAN; GUANINE NUCLEOTIDE BINDING PROTEIN; ONCOPROTEIN; PEPTIDE SYNTHASE; PROTEIN; UBIQUITIN PROTEIN LIGASE;

ALPHA ANTITRYPSIN DEFICIENCY; ALZHEIMER DISEASE; ARTICLE; CANCER; CELL NUCLEUS; CHIMERA; CYSTIC FIBROSIS; CYTOPLASM; CYTOTOXIC T LYMPHOCYTE; DEGENERATIVE DISEASE; DIABETES MELLITUS; DRUG EFFECT; ENZYME STRUCTURE; ENZYME SUBSTRATE; GENE THERAPY; HAPPY PUPPET SYNDROME; HUMAN; IMMUNOMODULATION; LIDDLE SYNDROME; METABOLIC DISORDER; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN TARGETING; TREATMENT INDICATION; TREATMENT PLANNING; UTERINE CERVIX CARCINOMA; VON HIPPEL LINDAU DISEASE; WILSON DISEASE; BIOLOGICAL MODEL; CHEMISTRY; FEMALE; GENETICS; MALE; METABOLISM; NEOPLASM; REVIEW; UTERINE CERVIX TUMOR;

EUKARYOTA;

ALZHEIMER DISEASE; ANGELMAN SYNDROME; BETA-TRANSDUCIN REPEAT-CONTAINING PROTEINS; CYSTIC FIBROSIS; FEMALE; GTP-BINDING PROTEINS; HEPATOLENTICULAR DEGENERATION; HIPPEL-LINDAU DISEASE; HUMANS; LIGASES; MALE; MODELS, BIOLOGICAL; NEOPLASMS; PARKINSON DISEASE; PEPTIDE SYNTHASES; PROTEINS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-CBL; SKP CULLIN F-BOX PROTEIN LIGASES; UBIQUITIN; UBIQUITIN-PROTEIN LIGASES; UTERINE CERVICAL NEOPLASMS;

EID: 0036395180     PISSN: 10967192     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1096-7192(02)00146-4     Document Type: Review

References (107)

1. A. Hershko, A. Ciechanover, The ubiquitin system, Annu. Rev. Biochem. 67 (1998) 425-479.
2. D. Voges, P. Zwickl, W. Baumeister, The 26S proteasome: a molecular machine designed for controlled proteolysis, Annu. Rev. Biochem. 68 (1999) 1015-1068.
3. C.M. Pickart, Mechanisms underlying ubiquitination, Annu. Rev. Biochem. 70 (2001) 503-533.
4. R.J. Deshaies, SCF and Cullin/Ring H2-based ubiquitin ligases, Annu. Rev. Cell Dev. Biol. 15 (1999) 435-467.
5. R. Verma, R.J. Deshaies, A proteasome howdunit: the case of the missing signal, Cell 101 (2000) 341-344.
6. P.K. Jackson, A.G. Eldridge, E. Freed, L. Furstenthal, J.Y. Hsu, B.K. Kaiser, J.D. Reimann, The lore of the RINGs: Substrate recognition and catalysis by ubiquitin ligases, Trends Cell Biol. 10 (2000) 429-439.
7. Z. Lu, S. Xu, C. Joazeiro, M.H. Cobb, T. Hunter, The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2, Mol. Cell 9 (2002) 945-956.
8. L. Coscoy, D.J. Sanchez, D. Ganem, A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition, J. Cell Biol. 155 (2001) 1265-1273.
9. L. Aravind, E.V. Koonin, The U box is a modi.ed RING finger - a common domain in ubiquitination, Curr. Biol. 10 (2000) R132-R134.
10. M. Scheffner, J.M. Huibregtse, R.D. Vierstra, P.M. Howley, The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53, Cell 75 (1993) 495-505.
11. A.M. Weissman, Themes and variations on ubiquitylation, Nat. Rev. Mol. Cell Biol. 2 (2001) 169-178.
12. A.J. Saurin, K.L. Borden, M.N. Boddy, P.S. Freemont, Does this have a familiar RING?, Trends Biochem. Sci. 21 (1996) 208-214.
13. D. Skowyra, K.L. Craig, M. Tyers, S.J. Elledge, J.W. Harper, F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex, Cell 91 (1997) 209-219.
14. R.M. Feldman, C.C. Correll, K.B. Kaplan, R.J. Deshaies, A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p, Cell 91 (1997) 221-230.
15. J.H. Seol, R.M. Feldman, W. Zachariae, A. Shevchenko, C.C. Correll, S. Lyapina, Y. Chi, M. Galova, J. Claypool, S. Sandmeyer, K. Nasmyth, R.J. Deshaies, Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF de.ne a ubiquitin ligase module that activates the E2 enzyme Cdc34, Genes Dev. 13 (1999) 1614-1626.
16. D. Skowyra, D.M. Koepp, T. Kamura, M.N. Conrad, R.C. Conaway, J.W. Conaway, S.J. Elledge, J.W. Harper, Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1, Science 284 (1999) 662-665.
17. N. Zheng, B.A. Schulman, L. Song, J.J. Miller, P.D. Jeffrey, P. Wang, C. Chu, D.M. Koepp, S.J. Elledge, M. Pagano, R.C. Conaway, J.W. Conaway, J.W. Harper, N.P. Pavletich, Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex, Nature 416 (2002) 703-709.
18. E.T. Kipreos, M. Pagano, The F-box protein family, Genome Biol. 1 (2000) 3002, REVIEWS.
19. R. Verma, R.M. Feldman, R.J. Deshaies, SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities, Mol. Biol. Cell 8 (1997) 1427-1437.
20. S. Elsasser, Y. Chi, P. Yang, J.L. Campbell, Phosphorylation controls timing of Cdc6p destruction: a biochemical analysis, Mol. Biol. Cell 10 (1999) 3263-3277.
21. Y. Chi, M.J. Huddleston, X. Zhang, R.A. Young, R.S. Annan, S.A. Carr, R.J. Deshaies, Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase, Genes Dev. 15 (2001) 1078-1092.
22. D. Kornitzer, B. Raboy, R.G. Kulka, G.R. Fink, Regulated degradation of the transcription factor Gcn4, EMBO J. 13 (1994) 6021-6030.
23. N. Valtz, M. Peter, Functional analysis of FAR1 in yeast, Methods Enzymol. 283 (1997) 350-365.
24. S.Y. Fuchs, A. Chen, Y. Xiong, Z.Q. Pan, Z. Ronai, HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IκB and β-catenin, Oncogene 18 (1999) 2039-2046.
25. J.T. Winston, P. Strack, P. Beer-Romero, C.Y. Chu, S.J. Elledge, J.W. Harper, The SCFβ-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IκBα and β-catenin and stimulates IκBα ubiquitination in vitro, Genes Dev. 13 (1999) 270-283.
26. A. Yaron, A. Hatzubai, M. Davis, I. Lavon, S. Amit, A.M. Manning, J.S. Andersen, M. Mann, F. Mercurio, Y. Ben-Neriah, Identification of the receptor component of the IκBα-ubiquitin ligase, Nature 396 (1998) 590-594.
27. T. Kamura, M.N. Conrad, Q. Yan, R.C. Conaway, J.W. Conaway, The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2, Genes Dev. 13 (1999) 2928-2933.
28. W. Krek, VHL takes HIF's breath away, Nat. Cell Biol. 2 (2000) E121-E123.
29. C.E. Stebbins, W.G. Kaelin Jr., N.P. Pavletich, Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function, Science 284 (1999) 455-461.
30. J.D. Singer, M. Gurian-West, B. Clurman, J.M. Roberts, Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells, Genes Dev. 13 (1999) 2375-2387.
31. P. Shiyanov, A. Nag, P. Raychaudhuri, Cullin 4A associates with the UV-damaged DNA-binding protein DDB, J. Biol. Chem. 274 (1999) 35309-35312.
32. R.C. Conaway, C.S. Brower, J. Conaway, Emerging roles of ubiquitin in transcription regulation, Science 296 (2002) 1254-1258.
33. J.M. Peters, The anaphase-promoting complex. Proteolysis in mitosis and beyond, Mol. Cell 9 (2002) 931-943.
34. J.D. Leverson, C.A. Joazeiro, A.M. Page, H. Huang, P. Hieter, T. Hunter, The APC11 RING-H2 finger mediates E2-dependent ubiquitination, Mol. Biol. Cell 11 (2000) 2315-2325.
35. P. Page AMand Hieter, The anaphase-promoting complex: new subunits and regulators, Annu. Rev. Biochem. 68 (1999) 583-609.
36. R. Visintin, S. Prinz, A. Amon, CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis, Science 278 (1997) 460-463.
37. K.L. Borden, P.S. Freemont, The RING finger domain: a recent example of a sequence-structure family, Curr. Opin. Struct. Biol. 6 (1996) 395-401.
38. R. Aasland, T.J. Gibson, A.F. Stewart, The PHD finger: implications for chromatin-mediated transcriptional regulation, Trends Biochem. Sci. 20 (1995) 56-59.
39. M. Gunduz, M. Ouchida, K. Fukushima, H. Hanafusa, T. Etani, S. Nishioka, K. Nishizaki, K. Shimizu, Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas, Cancer Res. 60 (2000) 3143-3146.
40. P. Saugier-Veber, N. Drouot, L.M. Wolf, J.M. Kuhn, T. Frebourg, H. Lefebvre, Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, Eur. J. Endocrinol. 144 (2001) 347-351.
41. S. Jacobson, L. Pillus, Modifying chromatin and concepts of cancer, Curr. Opin. Genet Dev. 9 (1999) 175-184.
42. U. Aapola, K. Kawasaki, H.S. Scott, J. Ollila, M. Vihinen, M. Heino, A. Shintani, S. Minoshima, K. Krohn, S.E. Antonarakis, N. Shimizu, J. Kudoh, P. Peterson, Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family, Genomics 65 (2000) 293-298.
43. A.D. Capili, D.C. Schultz, I.F. Rauscher, K.L. Borden, Solution structure of the PHD domain from the KAP-1 corepressor: structural determinants for PHD, RING and LIM zinc-binding domains, EMBO J. 20 (2001) 165-177.
44. P. Hawley-Nelson, K.H. Vousden, N.L. Hubbert, D.R. Lowy, J.T. Schiller, HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes, EMBO J. 8 (1989) 3905-3910.
45. C. Spruck, H. Strohmaier, M. Watson, A.P. Smith, A. Ryan, T.W. Krek, S.I. Reed, A CDK-independent function of mammalian Cks1: targeting of SCF (Skp2) to the CDK inhibitor p27Kip1, Mol. Cell 7 (2001) 639-650.
46. J.Y. Kato, M. Matsuoka, K. Polyak, J. Massague, C.J. Sherr, Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation, Cell 79 (1994) 487-496.
47. M. Loda, B. Cukor, S.W. Tam, P. Lavin, M. Fiorentino, G.F. Draetta, J.M. Jessup, M. Pagano, Increased proteasomedependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas, Nat. Med. 3 (1997) 231-234.
48. N. Jones, Structure and function of transcription factors, Semin. Cancer Biol. 1 (1990) 5-17.
49. P.L. Porter, K.E. Malone, P.J. Heagerty, G.M. Alexander, L.A. Gatti, E.J. Firpo, J.R. Daling, J.M. Roberts, Expression of cellcycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients, Nat. Med. 3 (1997) 222-225.
50. K. Nakayama, H. Nagahama, Y.A. Minamishima, M. Matsumoto, I. Nakamichi, K. Kitagawa, M. Shirane, R. Tsunematsu, T. Tsukiyama, N. Ishida, M. Kitagawa, S. Hatakeyama, Targeted disruption of Skp2 results in accumulation of cyclin E and p27 (Kip1), polyploidy and centrosome overduplication, EMBO J. 19 (2000) 2069-2081.
51. H. Strohmaier, C.H. Spruck, P. Kaiser, K.A. Won, O. Sangfelt, S.I. Reed, Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line, Nature 413 (2001) 316-322.
52. S. Hatakeyama, M. Kitagawa, K. Nakayama, M. Shirane, M. Matsumoto, K. Hattori, H. Higashi, H. Nakano, K. Okumura, K. Onoe, R.A. Good, Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1, Proc. Natl. Acad. Sci. USA 96 (1999) 3859-3863.
53. P. Polakis, Wnt signaling and cancer, Genes Dev. 14 (2000) 1837-1851.
54. H. Aberle, A. Bauer, J. Stappert, A. Kispert, R. Kemler, b-Catenin is a target for the ubiquitin-proteasome pathway, EMBO J. 16 (1997) 3797-3804.
55. V. Korinek, N. Barker, P.J. Morin, D. van Wichen, R. de Weger, K.W. Kinzler, B. Vogelstein, H. Clevers, Constitutive transcriptional activation by a β-catenin-Tcf complex in APC-/- colon carcinoma, Science 275 (1997) 1784-1787.
56. S. Amit, A. Hatzubai, Y. Birman, J.S. Andersen, E. Ben-Shushan, M. Mann, Y. Ben-Neriah, I. Alkalay, Axin-mediated CKI phosphorylation of β-catenin at Ser 45: a molecular switch for the Wnt pathway, Genes Dev. 16 (2002) 1066-1076.
57. Z. Chen, J. Hagler, V.J. Palombella, F. Melandri, D. Scherer, D. Ballard, T. Maniatis, Signal-induced site-specific phosphorylation targets IκBα to the ubiquitin-proteasome pathway, Genes Dev. 9 (1995) 1586-1597.
58. L. Deng, C. Wang, E. Spencer, L. Yang, A. Braun, J. You, C. Slaughter, C. Pickart, Z.J. Chen, Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain, Cell 103 (2000) 351-361.
59. J.R. Gnarra, K. Tory, Y. Weng, L. Schmidt, M.H. Wei, H. Li, F. Latif, S. Liu, F. Chen, F.M. Duh, et al., Mutations of the VHL tumour suppressor gene in renal carcinoma, Nat. Genet. 7 (1994) 85-90.
60. H. Yang, W.G. Kaelin Jr., Molecular pathogenesis of the von Hippel-Lindau hereditary cancer syndrome: implications for oxygen sensing, Cell Growth Differ. 12 (2001) 447-455.
61. 2 sensing, Science 292 (2001) 464-468.
62. A. Pause, S. Lee, K.M. Lonergan, R.D. Klausner, The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal, Proc. Natl. Acad. Sci. USA 95 (1998) 993-998.
63. B. Knebelmann, S. Ananth, H.T. Cohen, V.P. Sukhatme, Transforming growth factor a is a target for the von Hippel-Lindau tumor suppressor, Cancer Res. 58 (1998) 226-231.
64. M. Gorospe, J.M. Egan, B. Zbar, M. Lerman, L. Geil, I. Kuzmin, N.J. Holbrook, Protective function of von Hippel-Lindau protein against impaired protein processing in renal carcinoma cells, Mol. Cell Biol. 19 (1999) 1289-1300.
65. M. Ohh, R.L. Yauch, K.M. Lonergan, J.M. Whaley, A.O. Stemmer-Rachamimov, D.N. Louis, B.J. Gavin, N. Kley, W.G. Kaelin Jr., O. Iliopoulos, The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix, Mol. Cell 1 (1998) 959-968.
66. O. Iliopoulos, A.P. Levy, C. Jiang, W.G. Kaelin Jr., M.A. Goldberg, Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein, Proc. Natl. Acad. Sci. USA 93 (1996) 10595-10599.
67. G. Siemeister, K. Weindel, K. Mohrs, B. Barleon, G. Martiny-Baron, D. Marme, Reversion of deregulated expression of vascular endothelial growth factor in human renal carcinoma cells by von Hippel-Lindau tumor suppressor protein, Cancer Res. 56 (1996) 2299-2301.
68. C.A. Joazeiro, S.S. Wing, H. Huang, J.D. Leverson, T. Hunter, Y.C. Liu, The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase, Science 286 (1999) 309-312.
69. C.B. Thien, W.Y. Langdon, Cbl: many adaptations to regulate protein tyrosine kinases, Nat. Rev. Mol. Cell Biol. 2 (2001) 294-307.
70. A.Y. Tsygankov, A.M. Teckchandani, E.A. Feshchenko, G. Swaminathan, Beyond the RING: CBL proteins as multivalent adapters, Oncogene 20 (2001) 6382-6402.
71. Y. Ben-Neriah, Regulatory functions of ubiquitination in the immune system, Nat. Immunol. 3 (2002) 20-26.
72. A. Sanjay, W.C. Horne, R. Baron, The Cbl family: ubiquitin ligases regulating signaling by tyrosine kinases, Sci. STKE 2001 (2001) PE40.
73. T. Kishino, M. Lalande, J. Wagstaff, UBE3A/E6-AP mutations cause Angelman syndrome, Nat. Genet. 15 (1997) 70-73.
74. C.J. Cummings, E. Reinstein, Y. Sun, B. Antalffy, Y. Jiang, A. Ciechanover, H.T. Orr, A.L. Beaudet, H.Y. Zoghbi, Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice, Neuron 24 (1999) 879-892.
75. Y. Mizuno, N. Hattori, H. Matsumine, Neurochemical and neurogenetic correlates of Parkinson's disease, J. Neurochem. 71 (1998) 893-902.
76. K. Tanaka, T. Suzuki, T. Chiba, H. Shimura, N. Hattori, Y. Mizuno, Parkin is linked to the ubiquitin pathway, J. Mol. Med. 79 (2001) 482-494.
77. H. Shimura, N. Hattori, S. Kubo, Y. Mizuno, S. Asakawa, S. Minoshima, N. Shimizu, K. Iwai, T. Chiba, K. Tanaka, T. Suzuki, Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase, Nat. Genet. 25 (2000) 302-305.
78. M.H. Polymeropoulos, C. Lavedan, E. Leroy, S.E. Ide, A. Dehejia, A. Dutra, B. Pike, H. Root, J. Rubenstein, R. Boyer, E.S. Stenroos, S. Chandrasekharappa, A. Athanassiadou, T. Papapetropoulos, W.G. Johnson, A.M. Lazzarini, R.C. Duvoisin, G. Di Iorio, L.I. Golbe, R.L. Nussbaum, Mutation in the asynuclein gene identified in families with Parkinson's disease, Science 276 (1997) 2045-2047.
79. R. Kruger, W. Kuhn, T. Muller, D. Woitalla, M. Graeber, S. Kosel, H. Przuntek, J.T. Epplen, L. Schols, O. Riess, Ala30Promutation in the gene encoding α-synuclein in Parkinson's disease, Nat. Genet. 18 (1998) 106-108.
80. C.N. Larsen, B.A. Krantz, K.D. Wilkinson, Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases, Biochemistry 37 (1998) 3358-3368.
81. M.G. Spillantini, M.L. Schmidt, V.M. Lee, J.Q. Trojanowski, R. Jakes, M. Goedert, α-Synuclein in Lewy bodies, Nature 388 (1997) 839-840.
82. M.C. Bennett, J.F. Bishop, Y. Leng, P.B. Chock, T.N. Chase, M.M. Mouradian, Degradation of α-synuclein by proteasome, J. Biol. Chem. 274 (1999) 33855-33858.
83. S.W. Davies, M. Turmaine, B.A. Cozens, M. DiFiglia, A.H. Sharp, C.A. Ross, E. Scherzinger, E.E. Wanker, L. Mangiarini, G.P. Bates, Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation, Cell 90 (1997) 537-548.
84. P.J. Skinner, B.T. Koshy, C.J. Cummings, I.A. Klement, K. Helin, A. Servadio, H.Y. Zoghbi, H.T. Orr, Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures, Nature 389 (1997) 971-974.
85. S.B. Prusiner, Prions, Proc. Natl. Acad. Sci. USA 95 (1998) 13363-13383.
86. G. Lennox, J. Lowe, K. Morrell, M. Landon, R.J. Mayer, Ubiquitin is a component of neurofibrillary tangles in a variety of neurodegenerative diseases, Neurosci. Lett. 94 (1988) 211-217.
87. N.F. Bence, R.M. Sampat, R.R. Kopito, Impairment of the ubiquitin-proteasome system by protein aggregation, Science 292 (2001) 1552-1555.
88. T.J. Jensen, M.A. Loo, S. Pind, D.B. Williams, A.L. Goldberg, J.R. Riordan, Multiple proteolytic systems, including the proteasome, contribute to CFTR processing, Cell 83 (1995) 129-135.
89. M. Welsh, A.E. Smith, Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis, Cell 73 (1993) 1251-1254.
90. R. Greger, R. Schreiber, M. Mall, A. Wissner, A. Hopf, M. Briel, M. Bleich, R. Warth, K. Kunzelmann, Cystic fibrosis and CFTR, Pflugers Arch. 443 (Suppl. 1) (2001) S3-S7.
91. A.S. Payne, E.J. Kelly, J.D. Gitlin, Functional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutation, Proc. Natl. Acad. Sci. USA 95 (1998) 10854-10859.
92. + channel (ENaC) by ubiquitination, EMBO J. 16 (1997) 6325-6336.
93. S.I. Taylor, Lilly lecture: molecular mechanisms of insulin resistance. Lessons from patients with mutations in the insulinreceptor gene, Diabetes 41 (1992) 1473-1490.
94. J. Bass, C. Turck, M. Rouard, D.F. Steiner, Furin-mediated processing in the early secretory pathway: sequential cleavage and degradation of misfolded insulin receptors, Proc. Natl. Acad. Sci. USA 97 (2000) 11905-11909.
95. Y. Wu, I. Whitman, E. Molmenti, K. Moore, P. Hippenmeyer, D.H. Perlmutter, A lag in intracellular degradation of mutant α 1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ α 1-antitrypsin deficiency, Proc. Natl. Acad. Sci. USA 91 (1994) 014-018.
96. K.L. Rock, C. Gramm, L. Rothstein, K. Clark, R. Stein, L. Dick, D. Hwang, A.L. Goldberg, Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules, Cell 78 (1994) 761-771.
97. H.L. Ploegh, Viral strategies of immune evasion, Science 280 (1998) 248-253.
98. M.G. Masucci, I. Ernberg, Epstein-Barr virus: adaptation to a life within the immune system, Trends Microbiol. 2 (1994) 125-130.
99. R.L. Willey, F. Maldarelli, M.A. Martin, K. Strebel, Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4, J. Virol. 66 (1992) 7193-7200.
100. F. Margottin, S.P. Bour, H. Durand, L. Selig, S. Benichou, V. Richard, D. Thomas, K. Strebel, R. Benarous, A novel human WD protein, h-β TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif, Mol. Cell 1 (1998) 565-574.
101. P. Zhou, R. Bogacki, L. McReynolds, P.M. Howley, Harnessing the ubiquitination machinery to target the degradation of specific cellular proteins, Mol. Cell 6 (2000) 751-756.
102. K.M. Sakamoto, K.B. Kim, A. Kumagai, F. Mercurio, C.M. Crews, R.J. Deshaies, Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation, Proc. Natl. Acad. Sci. USA 98 (2001) 8554-8559.
103. N. Zheng, P. Wang, P.D. Jeffrey, N.P. Pavletich, Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitinprotein ligases, Cell 102 (2000) 533-539.
104. A. Citri, I. Alroy, S. Lavi, C. Rubin, W. Xu, N. Grammatikakis, C. Patterson, L. Neckers, D.W. Fry, Y. Yarden, Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy, EMBO J. 21 (2002) 2407-2417.
105. S.D. Kuduk, T.C. Harris, F.F. Zheng, L. Sepp-Lorenzino, Q. Ouerfelli, N. Rosen, S.J. Danishefsky, Synthesis and evaluation of geldanamycin-testosterone hybrids, Bioorg. Med. Chem. Lett. 10 (2000) 1303-1306.
106. F.F. Zheng, S.D. Kuduk, G. Chiosis, P.N. Munster, L. Sepp-Lorenzino, S.J. Danishefsky, N. Rosen, Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases, Cancer Res. 60 (2000) 2090-2094.
107. S.D. Kuduk, F.F. Zheng, L. Sepp-Lorenzino, N. Rosen, S.J. Danishefsky, Synthesis and evaluation of geldanamycin-estradiol hybrids, Bioorg. Med. Chem. Lett. 9 (1999) 1233-1238.