Disassembly of Lys11 and mixed linkage polyubiquitin conjugates provides insights into function of proteasomal deubiquitinases Rpn11 and Ubp6

Journal of Biological Chemistry

Volumn 290, Issue 8, 2015, Pages 4688-4704

  Mansour, Wissam ^a   Nakasone, Mark A ^a,b   Von Delbrück, Maximilian ^c   Yu, Zanlin ^a   Krutauz, Daria ^a   Reis, Noa ^a   Kleifeld, Oded ^d   Sommer, Thomas ^c   Fushman, David ^b   Glickman, Michael H ^a  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b Bldg 142   (United States)

^c MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^d MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

BIOCHEMISTRY; BIOLOGY;

26 S PROTEASOME; DECONJUGATION; POLYUBIQUITIN; PROTEASOMES;

PROTEOLYSIS;

DEUBIQUITINASE; LYSINE; POLYUBIQUITIN; PROTEASOME; PROTEIN RPN11; PROTEIN UBP6; UNCLASSIFIED DRUG; PROTEINASE; RPN11 PROTEIN, S CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEIN; UBP6 PROTEIN, S CEREVISIAE;

ARTICLE; CARBOXY TERMINAL SEQUENCE; CONJUGATION; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME DEGRADATION; ENZYME MECHANISM; ENZYME SPECIFICITY; ENZYME SUBSTRATE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN DISASSEMBLY; UBIQUITINATION; GENETICS; METABOLISM; PROTEIN DEGRADATION; PROTEIN TERTIARY STRUCTURE; SACCHAROMYCES CEREVISIAE;

ENDOPEPTIDASES; LYSINE; POLYUBIQUITIN; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN STRUCTURE, TERTIARY; PROTEOLYSIS; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

EID: 84928712769     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.568295     Document Type: Article

References (101)

1. Hershko, A., Ciechanover, A., and Varshavsky, A. (2000) Basic Medical Research Award: the ubiquitin system. Nat. Med. 6, 1073-1081
2. Komander, D. (2009) The emerging complexity of protein ubiquitination. Biochem. Soc Trans 37, 937-953
3. Finley, D. (2009) Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu. Rev. Biochem. 78, 477-513
4. Glickman, M. H., and Ciechanover, A. (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 82, 373-428
5. Ikeda, F., and Dikic, I. (2008) Atypical ubiquitin chains: new molecular signals. EMBO Rep. 9, 536-542
6. Pickart, C. M., and Fushman, D. (2004) Polyubiquitin chains: polymeric protein signals. Curr. Opin. Chem. Biol. 8, 610-616
7. Kravtsova-Ivantsiv, Y., Sommer, T., and Ciechanover, A. (2013) The lysine48- based polyubiquitin chain proteasomal signal: not a single child anymore. Angew Chem. Int. Ed. Engl. 52, 192-198
8. Volk, S., Wang, M., and Pickart, C. M. (2005) Chemical and genetic strategies for manipulating polyubiquitin chain structure. Methods Enzymol. 399, 3-20
9. Reyes-Turcu, F. E., Ventii, K. H., and Wilkinson, K. D. (2009) Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu. Rev. Biochem. 78, 363-397
10. Komander, D. (2010) Mechanism, specificity and structure of the deubiquitinases. Subcell. Biochem. 54, 69-87
11. Lee, M. J., Lee, B. H., Hanna, J., King, R. W., and Finley, D. (2011) Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes. Mol. Cell Proteomics 10.1074/mcp.R110.003871
12. Eletr, Z. M., and Wilkinson, K. D. (2014) Regulation of proteolysis by human deubiquitinating enzymes. Biochim. Biophys. Acta 1843, 114-128
13. Ziv, I., Matiuhin, Y., Kirkpatrick, D. S., Erpapazoglou, Z., Leon, S., Pantazopoulou, M., Kim, W., Gygi, S. P., Haguenauer-Tsapis, R., Reis, N., Glickman, M. H., and Kleifeld, O. (2011) A perturbed ubiquitin landscape distinguishes between ubiquitin in trafficking and in proteolysis. Mol. Cell Proteomics 10, 10.1074/mcp.M111.009753
14. Dammer, E. B., Na, C. H., Xu, P., Seyfried, N. T., Duong, D. M., Cheng, D., Gearing, M., Rees, H., Lah, J. J., Levey, A. I., Rush, J., and Peng, J. (2011) Polyubiquitin linkage profiles in three models of proteolytic stress suggest the etiology of Alzheimer disease. J. Biol. Chem. 286, 10457-10465
15. Dikic, I., and Dötsch, V. (2009) Ubiquitin linkages make a difference. Nat. Struct. Mol. Biol. 16, 1209-1210
16. Kim, W., Bennett, E. J., Huttlin, E. L., Guo, A., Li, J., Possemato, A., Sowa, M. E., Rad, R., Rush, J., Comb, M. J., Harper, J. W., and Gygi, S. P. (2011) Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell 44, 325-340
17. Matsumoto, M. L., Wickliffe, K. E., Dong, K. C., Yu, C., Bosanac, I., Bustos, D., Phu, L., Kirkpatrick, D. S., Hymowitz, S. G., Rape, M., Kelley, R. F., and Dixit, V. M. (2010) K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody. Mol. Cell 39, 477-484
18. Meyer, H. J., and Rape, M. (2014) Enhanced protein degradation by branched ubiquitin chains. Cell 157, 910-921
19. Locke, M., Toth, J. I., and Petroski, M. D. (2014) Lys11- and Lys48-linked ubiquitin chains interact with p97 during endoplasmic-reticulum-associated degradation. Biochem. J. 459, 205-216
20. Glickman, M. H., Rubin, D. M., Fried, V. A., and Finley, D. (1998) The regulatory particle of the Saccharomyces cerevisiae proteasome. Mol. Cell. Biol. 18, 3149-3162
21. Tanaka, K., Mizushima, T., and Saeki, Y. (2012) The proteasome: molecular machinery and pathophysiological roles. Biol. Chem. 393, 217-234
22. Ambroggio, X. I., Rees, D. C., and Deshaies, R. J. (2004) JAMM: a metalloprotease- like zinc site in the proteasome and signalosome. PLoS Biol. 2, E2
23. Verma, R., Aravind, L., Oania, R., McDonald, W. H., Yates, J. R., 3rd, Koonin, E. V., and Deshaies, R. J. (2002) Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science 298, 611-615
24. Koulich, E., Li, X., and DeMartino, G. N. (2008) Relative structural and functional roles of multiple deubiquitylating proteins associated with mammalian 26S proteasome. Mol. Biol. Cell 19, 1072-1082
25. Hu, M., Li, P., Song, L., Jeffrey, P. D., Chenova, T. A., Wilkinson, K. D., Cohen, R. E., and Shi, Y. (2005) Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. EMBO J. 24, 3747-3756
26. Rosenzweig, R., Bronner, V., Zhang, D., Fushman, D., and Glickman, M. H. (2012) Rpn1 and Rpn2 coordinate ubiquitin processing factors at proteasome. J. Biol. Chem. 287, 14659-14671
27. +, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function. BMC Biochem. 3, 28
28. Pathare, G. R., Nagy, I.,͆ ledź, P., Anderson, D. J., Zhou, H. J., Pardon, E., Steyaert, J., Förster, F., Bracher, A., and Baumeister, W. (2014) Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11. Proc. Natl. Acad. Sci. U.S.A. 111, 2984-2989
29. Worden, E. J., Padovani, C., and Martin, A. (2014) Structure of the Rpn11-Rpn8 dimer reveals mechanisms of substrate deubiquitination during proteasomal degradation. Nat. Struct. Mol. Biol. 21, 220-227
30. Bhattacharyya, S., Yu, H., Mim, C., and Matouschek, A. (2014) Regulated protein turnover: snapshots of the proteasome in action. Nat. Rev. Mol. Cell Biol. 15, 122-133
31. Matyskiela, M. E., Lander, G. C., and Martin, A. (2013) Conformational switching of the 26S proteasome enables substrate degradation. Nat. Struct. Mol. Biol. 20, 781-788
32. Peth, A., Kukushkin, N., Bossé, M., and Goldberg, A. L. (2013) Ubiquitinated proteins activate the proteasomal ATPases by binding to Usp14 or Uch37 homologs. J. Biol. Chem. 288, 7781-7790
33. Peth, A., Besche, H. C., and Goldberg, A. L. (2009) Ubiquitinated proteins activate the proteasome by binding to Usp14/Ubp6, which causes 20S gate opening. Mol. Cell 36, 794-804
34. Hanna, J., Hathaway, N. A., Tone, Y., Crosas, B., Elsasser, S., Kirkpatrick, D. S., Leggett, D. S., Gygi, S. P., King, R. W., and Finley, D. (2006) Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell 127, 99-111
35. Yao, T., and Cohen, R. E. (2002) A cryptic protease couples deubiquitination and degradation by the proteasome. Nature 419, 403-407
36. + complexes: BRISC-associated Brcc36 and proteasomal Poh1. EMBO J. 28, 621-631
37. Guterman, A., and Glickman, M. H. (2004) Complementary roles for Rpn11 and Ubp6 in deubiquitination and proteolysis by the proteasome. J. Biol. Chem. 279, 1729-1738
38. Glickman, M. H., and Adir, N. (2004) The proteasome and the delicate balance between destruction and rescue. PLoS Biol. 2, E13
39. Inobe, T., and Matouschek, A. (2014) Paradigms of protein degradation by the proteasome. Curr. Opin. Struct. Biol. 24, 156-164
40. Peth, A., Uchiki, T., and Goldberg, A. L. (2010) ATP-dependent steps in the binding of ubiquitin conjugates to the 26S proteasome that commit to degradation. Mol. Cell 40, 671-681
41. Leggett, D. S., Hanna, J., Borodovsky, A., Crosas, B., Schmidt, M., Baker, R. T., Walz, T., Ploegh, H., and Finley, D. (2002) Multiple associated proteins regulate proteasome structure and function. Mol. Cell 10, 495-507
42. Matiuhin, Y., Kirkpatrick, D. S., Ziv, I., Kim, W., Dakshinamurthy, A., Kleifeld, O., Gygi, S. P., Reis, N., and Glickman, M. H. (2008) Extraproteasomal Rpn10 restricts access of the polyubiquitin-binding protein Dsk2 to proteasome. Mol. Cell 32, 415-425
43. Lander, G. C., Estrin, E., Matyskiela, M. E., Bashore, C., Nogales, E., and Martin, A. (2012) Complete subunit architecture of the proteasome regulatory particle. Nature 482, 186-191
44. Rogov, V. V., Rozenknop, A., Rogova, N. Y., Löhr, F., Tikole, S., Jaravine, V., Guntert, P., Dikic, I., and Dötsch, V. (2012) A universal expression tag for structural and functional studies of proteins. Chembiochem 13, 959-963
45. Pickart, C. M., and Raasi, S. (2005) Controlled synthesis of polyubiquitin chains. Methods Enzymol. 399, 21-36
46. Bagola, K., von Delbrück, M., Dittmar, G., Scheffner, M., Ziv, I., Glickman, M. H., Ciechanover, A., and Sommer, T. (2013) Ubiquitin binding by a CUE domain regulates ubiquitin chain formation by ERAD E3 ligases. Mol. Cell 50, 528-539
47. Berndsen, C. E., and Wolberger, C. (2011) A spectrophotometric assay for conjugation of ubiquitin and ubiquitin-like proteins. Anal. Biochem. 418, 102-110
48. Nakasone, M. A., Livnat-Levanon, N., Glickman, M. H., Cohen, R. E., and Fushman, D. (2013) Mixed-linkage ubiquitin chains send mixed messages. Structure 21, 727-740
49. Castañeda, C. A., Kashyap, T. R., Nakasone, M. A., Krueger, S., and Fushman, D. (2013) Unique structural, dynamical, and functional properties of k11-linked polyubiquitin chains. Structure 21, 1168-1181
50. Cannon, J., Nakasone, M., Fushman, D., and Fenselau, C. (2012) Proteomic identification and analysis of K63-linked ubiquitin conjugates. Anal. Chem. 84, 10121-10128
51. Keller, A., Eng, J., Zhang, N., Li, X. J., and Aebersold, R. (2005) A uniform proteomics MS/MS analysis platform utilizing open XML file formats. Mol. Syst. Biol. 1, 2005.0017
52. Fu, H., Reis, N., Lee, Y., Glickman, M. H., and Vierstra, R. D. (2001) Subunit interaction maps for the regulatory particle of the 26S proteasome and the COP9 signalosome. EMBO J. 20, 7096-7107
53. Lasker, K., Förster, F., Bohn, S., Walzthoeni, T., Villa, E., Unverdorben, P., Beck, F., Aebersold, R., Sali, A., and Baumeister, W. (2012) Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach. Proc. Natl. Acad. Sci. U.S.A. 109, 1380-1387
54. Glickman, M. H., Rubin, D. M., Larsen, C. N., and Finley, D. (2000) in Proteasomes: The World of Regultory Proteolysis (Hilt, W., and Wolf, D. H., eds) pp. 71-90, Eurekah.com/Landes Bioscience Publishing Co., Georgetown, TX
55. Leggett, D. S., Glickman, M. H., and Finley, D. (2005) Purification of proteasomes, proteasome subcomplexes, and proteasome-associated proteins from budding yeast. Methods Mol. Biol. 301, 57-70
56. Jacobson, A. D., Zhang, N. Y., Xu, P., Han, K. J., Noone, S., Peng, J., and Liu, C. W. (2009) The lysine 48 and lysine 63 ubiquitin conjugates are processed differently by the 26 S proteasome. J. Biol. Chem. 284, 35485-35494
57. Nathan, J. A., Kim, H. T., Ting, L., Gygi, S. P., and Goldberg, A. L. (2013) Why do cellular proteins linked to K63-polyubiquitin chains not associate with proteasomes? EMBO J. 32, 552-565
58. Cooper, E. M., Boeke, J. D., and Cohen, R. E. (2010) Specificity of the BRISC deubiquitinating enzyme is not due to selective binding to Lys63-linked polyubiquitin. J. Biol. Chem. 285, 10344-10352
59. Sato, Y., Yoshikawa, A., Yamagata, A., Mimura, H., Yamashita, M., Ookata, K., Nureki, O., Iwai, K., Komada, M., and Fukai, S. (2008) Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains. Nature 455, 358-362
60. Lee, B. H., Lee, M. J., Park, S., Oh, D. C., Elsasser, S., Chen, P. C., Gartner, C., Dimova, N., Hanna, J., Gygi, S. P., Wilson, S. M., King, R. W., and Finley, D. (2010) Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 467, 179-184
61. Lee, B. H., Finley, D., and King, R. W. (2012) A high-throughput screening method for identification of inhibitors of the deubiquitinating enzyme USP14. Curr. Protoc. Chem. Biol. 4, 311-330
62. Krutauz, D., Reis, N., Nakasone, M. A., Siman, P., Zhang, D., Kirkpatrick, D. S., Gygi, S. P., Brik, A., Fushman, D., and Glickman, M. H. (2014) Extended ubiquitin species are protein-based DUB inhibitors. Nat. Chem. Biol. 10, 664-670
63. D'Arcy, P., and Linder, S. (2012) Proteasome deubiquitinases as novel targets for cancer therapy. Int. J. Biochem. Cell Biol. 44, 1729-1738
64. D'Arcy, P., Brnjic, S., Olofsson, M. H., Fryknäs, M., Lindsten, K., De Cesare, M., Perego, P., Sadeghi, B., Hassan, M., Larsson, R., and Linder, S. (2011) Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat. Med. 17, 1636-1640
65. Hanna, J., Leggett, D. S., and Finley, D. (2003) Ubiquitin depletion as a key mediator of toxicity by translational inhibitors. Mol. Cell. Biol. 23, 9251-9261
66. Anderson, C., Crimmins, S., Wilson, J. A., Korbel, G. A., Ploegh, H. L., and Wilson, S. M. (2005) Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice. J. Neurochem. 95, 724-731
67. Shabek, N., Herman-Bachinsky, Y., Buchsbaum, S., Lewinson, O., Haj- Yahya, M., Hejjaoui, M., Lashuel, H. A., Sommer, T., Brik, A., and Ciechanover, A. (2012) The size of the proteasomal substrate determines whether its degradation will be mediated by mono- or polyubiquitylation. Mol. Cell 48, 87-97
68. Fushman, D., and Wilkinson, K. D. (2011) Structure and recognition of polyubiquitin chains of different lengths and linkage. F1000 Biol. Rep. 3, 26
69. Lingaraju, G. M., Bunker, R. D., Cavadini, S., Hess, D., Hassiepen, U., Renatus, M., Fischer, E. S., and Thomä, N. H. (2014) Crystal structure of the human COP9 signalosome. Nature 512, 161-165
70. Rinaldi, T., Hofmann, L., Gambadoro, A., Cossard, R., Livnat-Levanon, N., Glickman, M. H., Frontali, L., and Delahodde, A. (2008) Dissection of the carboxyl-terminal domain of the proteasomal subunit Rpn11 in maintenance of mitochondrial structure and function. Mol. Biol. Cell 19, 1022-1031
71. Kim, H. T., Kim, K. P., Lledias, F., Kisselev, A. F., Scaglione, K. M., Skowyra, D., Gygi, S. P., and Goldberg, A. L. (2007) Certain pairs of ubiquitinconjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ubiquitin chains containing all possible isopeptide linkages. J. Biol. Chem. 282, 17375-17386
72. Varadan, R., Walker, O., Pickart, C., and Fushman, D. (2002) Structural properties of polyubiquitin chains in solution. J. Mol. Biol. 324, 637-647
73. Schaefer, J. B., and Morgan, D. O. (2011) Protein-linked ubiquitin chain structure restricts activity of deubiquitinating enzymes. J. Biol. Chem. 286, 45186-45196
74. Thrower, J. S., Hoffman, L., Rechsteiner, M., and Pickart, C. M. (2000) Recognition of the polyubiquitin proteolytic signal. EMBO J. 19, 94-102
75. Wickliffe, K. E., Williamson, A., Meyer, H. J., Kelly, A., and Rape, M. (2011) K11-linked ubiquitin chains as novel regulators of cell division. Trends Cell Biol. 21, 656-663
76. Xu, P., Duong, D. M., Seyfried, N. T., Cheng, D., Xie, Y., Robert, J., Rush, J., Hochstrasser, M., Finley, D., and Peng, J. (2009) Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137, 133-145
77. Lin, D. Y., Diao, J., Zhou, D., and Chen, J. (2011) Biochemical and structural studies of a HECT-like ubiquitin ligase from Escherichia coli O157 H7. J. Biol. Chem. 286, 441-449
78. Ben-Saadon, R., Zaaroor, D., Ziv, T., and Ciechanover, A. (2006) The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity. Mol. Cell 24, 701-711
79. Kim, H. T., Kim, K. P., Uchiki, T., Gygi, S. P., and Goldberg, A. L. (2009) S5a promotes protein degradation by blocking synthesis of nondegradable forked ubiquitin chains. EMBO J. 28, 1867-1877
80. Qin, S., Wang, Q., Ray, A., Wani, G., Zhao, Q., Bhaumik, S. R., and Wani, A. A. (2009) Sem1p and Ubp6p orchestrate telomeric silencing by modulating histone H2B ubiquitination and H3 acetylation. Nucleic Acids Res. 37, 1843-1853
81. Wu, N., Liu, C., Bai, C., Han, Y. P., Cho, W. C., and Li, Q. (2013) Overexpression of deubiquitinating enzyme USP14 in lung adenocarcinoma promotes proliferation through the accumulation of β-catenin. Int. J. Mol. Sci. 14, 10749-10760
82. Jung, H., Kim, B. G., Han, W. H., Lee, J. H., Cho, J. Y., Park, W. S., Maurice, M. M., Han, J. K., Lee, M. J., Finley, D., and Jho, E. H. (2013) Deubiquitination of dishevelled by Usp14 is required for Wnt signaling. Oncogenesis 2, e64
83. Butler, L. R., Densham, R. M., Jia, J., Garvin, A. J., Stone, H. R., Shah, V., Weekes, D., Festy, F., Beesley, J., and Morris, J. R. (2012) The proteasomal de-ubiquitinating enzyme POH1 promotes the double-strand DNA break response. EMBO J. 31, 3918-3934
84. Feng, L., Wang, J., and Chen, J. (2010) The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments. J. Biol. Chem. 285, 30982-30988
85. Patterson-Fortin, J., Shao, G., Bretscher, H., Messick, T. E., and Greenberg, R. A. (2010) Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex. J. Biol. Chem. 285, 30971-30981
86. Schrader, E. K., Harstad, K. G., and Matouschek, A. (2009) Targeting proteins for degradation. Nat. Chem. Biol. 5, 815-822
87. Kraut, D. A., Prakash, S., and Matouschek, A. (2007) To degrade or release: ubiquitin-chain remodeling. Trends Cell Biol. 17, 419-421
88. da Fonseca, P. C., He, J., and Morris, E. P. (2012) Molecular model of the human 26S proteasome. Mol. Cell 46, 54-66
89. Beck, F., Unverdorben, P., Bohn, S., Schweitzer, A., Pfeifer, G., Sakata, E., Nickell, S., Plitzko, J. M., Villa, E., Baumeister, W., and Förster, F. (2012) Near-atomic resolution structural model of the yeast 26S proteasome. Proc. Natl. Acad. Sci. U.S.A. 109, 14870-14875
90. Chandra, A., Chen, L., and Madura, K. (2010) Synthetic lethality of rpn11-1 rpn10 is linked to altered proteasome assembly and activity. Curr. Genet. 56, 543-557
91. Rinaldi, T., Pick, E., Gambadoro, A., Zilli, S., Maytal-Kivity, V., Frontali, L., and Glickman, M. H. (2004) Participation of the proteasomal lid subunit Rpn11 in mitochondrial morphology and function is mapped to a distinct C-terminal domain. Biochem. J. 381, 275-285
92. Goldberg, A. L. (2012) Development of proteasome inhibitors as research tools and cancer drugs. J. Cell Biol. 199, 583-588
93. Liu, N., Liu, C., Li, X., Liao, S., Song, W., Yang, C., Zhao, C., Huang, H., Guan, L., Zhang, P., Liu, S., Hua, X., Chen, X., Zhou, P., Lan, X., Yi, S., Wang, S., Wang, X., Dou, Q. P., and Liu, J. (2014) A novel proteasome inhibitor suppresses tumor growth via targeting both 19S proteasome deubiquitinases and 20S proteolytic peptidases. Sci. Rep. 4, 5240
94. Schmidt, M., and Finley, D. (2014) Regulation of proteasome activity in health and disease. Biochim. Biophys. Acta 1843, 13-25
95. Tonoki, A., Kuranaga, E., Tomioka, T., Hamazaki, J., Murata, S., Tanaka, K., and Miura, M. (2009) Genetic evidence linking age-dependent attenuation of the 26S proteasome with the aging process. Mol. Cell. Biol. 29, 1095-1106
96. Gallery, M., Blank, J. L., Lin, Y., Gutierrez, J. A., Pulido, J. C., Rappoli, D., Badola, S., Rolfe, M., and Macbeth, K. J. (2007) The JAMM motif of human deubiquitinase Poh1 is essential for cell viability. Mol. Cancer Ther. 6, 262-268
97. Tian, Z., D'Arcy, P., Wang, X., Ray, A., Tai, Y. T., Hu, Y., Carrasco, R. D., Richardson, P., Linder, S., Chauhan, D., and Anderson, K. C. (2014) A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood 123, 706-716
98. Nag, D. K., and Finley, D. (2012) A small-molecule inhibitor of deubiquitinating enzyme USP14 inhibits Dengue virus replication. Virus Res. 165, 103-106
99. Kapuria, V., Peterson, L. F., Fang, D., Bornmann, W. G., Talpaz, M., and Donato, N. J. (2010) Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 70, 9265-9276
100. Eddins, M. J., Varadan, R., Fushman, D., Pickart, C. M., and Wolberger, C. (2007) Crystal structure and solution NMR studies of Lys48-linked tetraubiquitin at neutral pH. J. Mol. Biol. 367, 204-211
101. Datta, A. B., Hura, G. L., and Wolberger, C. (2009) The structure and conformation of Lys63-linked tetraubiquitin. J. Mol. Biol. 392, 1117-1124