Mechanisms of proteasome inhibitor action and resistance in cancer

Drug Resistance Updates

Volumn 11, Issue 4-5, 2008, Pages 164-179

  McConkey, David J ^a   Zhu, Keyi ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Autophagy; Bcl2 family; BIP; elf2 ; Grp78; NF B; p53; Pancreas; Pancreatic cancer; Unfolded protein response (UPR)

Indexed keywords

BORTEZOMIB; CARFILZOMIB; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PR 171; PROTEASOME INHIBITOR; PROTEIN BCL 2; PROTEIN P53; REACTIVE OXYGEN METABOLITE; SALINOSPORAMIDE A; UNCLASSIFIED DRUG;

AGGRESOME; ANGIOGENESIS; ARTICLE; AUTOPHAGY; CANCER CELL; CANCER RESISTANCE; CELL DEATH; DRUG ACTIVITY; DRUG MECHANISM; ENDOPLASMIC RETICULUM STRESS; MANTLE CELL LYMPHOMA; MULTIPLE MYELOMA; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN FOLDING;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CYSTEINE PROTEINASE INHIBITORS; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS; NF-KAPPA B; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN FOLDING; TREATMENT OUTCOME;

EID: 53049083867     PISSN: 13687646     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drup.2008.08.002     Document Type: Article

References (181)

1. Adams J. Development of the proteasome inhibitor PS-341. Oncologist 7 (2002) 9-16
2. Adams J. The development of proteasome inhibitors as anticancer drugs. Cancer Cell 5 (2004) 417-421
3. Adams J., Palombella V.J., Sausville E.A., et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 59 (1999) 2615-2622
4. Aghdassi A., Phillips P., Dudeja V., et al. Heat shock protein 70 increases tumorigenicity and inhibits apoptosis in pancreatic adenocarcinoma. Cancer Res. 67 (2007) 616-625
5. Altun M., Galardy P.J., Shringarpure R., et al. Effects of PS-341 on the activity and composition of proteasomes in multiple myeloma cells. Cancer Res. 65 (2005) 7896-7901
6. An J., and Rettig M.B. Epidermal growth factor receptor inhibition sensitizes renal cell carcinoma cells to the cytotoxic effects of bortezomib. Mol. Cancer Ther. 6 (2007) 61-69
7. Bahlis N.J., King A.M., Kolonias D., et al. CD28-mediated regulation of multiple myeloma cell proliferation and survival. Blood 109 (2007) 5002-5010
8. Beg A.A., and Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 274 (1996) 782-784
9. Bennett E.J., Bence N.F., Jayakumar R., and Kopito R.R. Global impairment of the ubiquitin-proteasome system by nuclear or cytoplasmic protein aggregates precedes inclusion body formation. Mol. Cell 17 (2005) 351-365
10. Bennett E.J., Shaler T., Gonzalez-Zulueta M., et al. Cellular mechanisms of protein quality control. Rinsho Shinkeigaku 46 (2006) 805
11. Birle D.C., and Hedley D.W. Suppression of the hypoxia-inducible factor-1 response in cervical carcinoma xenografts by proteasome inhibitors. Cancer Res. 67 (2007) 1735-1743
12. Bross P.F., Kane R., Farrell A.T., et al. Approval summary for bortezomib for injection in the treatment of multiple myeloma. Clin. Cancer Res. 10 (2004) 3954-3964
13. Busse A., Kraus M., Na I.K., et al. Sensitivity of tumor cells to proteasome inhibitors is associated with expression levels and composition of proteasome subunits. Cancer 112 (2008) 659-670
14. Canfield S.E., Zhu K., Williams S.A., McConkey D.J., et al. Bortezomib inhibits docetaxel-induced apoptosis via a p21-dependent mechanism in human prostate cancer cells. Mol. Cancer Ther. 5 (2006) 2043-2050
15. Cantley L.C., and Neel B.G. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc. Natl. Acad. Sci. USA 96 (1999) 4240-4245
16. Cascone T., Morelli M.P., Morgillo F., et al. Synergistic anti-proliferative and pro-apoptotic activity of combined therapy with bortezomib, a proteasome inhibitor, with anti-epidermal growth factor receptor (EGFR) drugs in human cancer cells. J. Cell Physiol. 216 (2008) 698-707
17. Catley L., Anderson K.C., et al. Velcade and vitamin C: too much of a good thing?. Clin. Cancer Res. 12 (2006) 3-4
18. Chauhan D., Catley L., Li G., et al. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from bortezomib. Cancer Cell 8 (2005) 407-419
19. Chauhan D., Hideshima T., Anderson K.C., et al. A novel proteasome inhibitor NPI-0052 as an anticancer therapy. Br. J. Cancer 95 (2006) 961-965
20. Chauhan D., Li G., Shringarpure R., Podar K., Ohtake Y., Hideshima T., and Anderson K.C. Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells. Cancer Res. 63 (2003) 6174-6177
21. Chauhan D., Singh A., Brahmandam M., et al. Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma. Blood 111 (2008) 1654-1664
22. Chauhan D., Velankar M., Brahmandam M., et al. A novel Bcl-2/Bcl-X(L)/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma. Oncogene 26 (2007) 2374-2380
23. Chen L., Willis S.N., Wei A., et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol. Cell 17 (2005) 393-403
24. Cusack Jr. J.C., Liu R., Houston M., et al. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res. 61 (2001) 3535-3540
25. Dai Y., Rahmani M., and Grant S. Proteasome inhibitors potentiate leukemic cell apoptosis induced by the cyclin-dependent kinase inhibitor flavopiridol through a SAPK/JNK- and NF-kappaB-dependent process. Oncogene 22 (2003) 7108-7122
26. Davenport E.L., Moore H.E., Dunlop A.S., et al. Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cells. Blood 110 (2007) 2641-2649
27. Davenport E.L., Morgan G.J., Davies F.E., et al. Untangling the unfolded protein response. Cell Cycle 7 (2008) 865-869
28. Dejardin E. The alternative NF-kappaB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochem. Pharmacol. 72 (2006) 1161-1179
29. Demo S.D., Kirk C.J., Aujay M.A., et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 67 (2007) 6383-6391
30. Deng J., Lu P.D., Zhang Y., et al. Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2. Mol. Cell Biol. 24 (2004) 10161-10168
31. Ding W.X., and Yin X.M. Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome. Autophagy 4 (2007) 141-150
32. Ding W.X., Ni H.M., Gao W., et al. Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J. Biol. Chem. 282 (2007) 4702-4710
33. Ding W.X., Ni H.M., Gao W., et al. Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am. J. Pathol. 171 (2007) 513-524
34. Drexler H.C. Activation of the cell death program by inhibition of proteasome function. Proc. Natl. Acad. Sci. USA 94 (1997) 855-860
35. Elliott P.J., Soucy T.A., Pien C.S., Adams J., and Lightcap E.S. Assays for proteasome inhibition. Methods Mol. Med. 85 (2003) 163-172
36. Evan G.I., Brown L., Whyte M., and Harrington E. Apoptosis and the cell cycle. Curr. Opin. Cell Biol. 7 (1995) 825-834
37. Fatokun A.A., Stone T.W., and Smith R.A. Oxidative stress in neurodegeneration and available means of protection. Front Biosci. 13 (2008) 3288-3311
38. Feling R.H., Buchanan G.O., Mincer T.J., Kauffman C.A., Jensen P.R., and Fenical W. Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora. Angew. Chem. Int. Ed. Engl. 42 (2003) 355-357
39. Fernandez Y., Verhaegen M., Miller T.P., et al. Differential regulation of Noxa in normal melanocytes and melanoma cells by proteasome inhibition: therapeutic implications. Cancer Res. 65 (2005) 6294-6304
40. Fratta P., Engel W.K., McFerrin J., Davies K.J., Lin S.W., and Askanas V. Proteasome inhibition and aggresome formation in sporadic inclusion-body myositis and in amyloid-beta precursor protein-overexpressing cultured human muscle fibers. Am. J. Pathol. 167 (2005) 517-526
41. Fribley A., Zeng Q., and Wang C.Y. Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Mol. Cell Biol. 24 (2004) 9695-9704
42. Fuchs D., Berges C., Opelz G., Daniel V., and Naujokat C. Increased expression and altered subunit composition of proteasomes induced by continuous proteasome inhibition establish apoptosis resistance and hyperproliferation of Burkitt lymphoma cells. J. Cell Biochem. 103 (2008) 270-283
43. Garber K. Cancer research. Taking garbage in, tossing cancer out?. Science 295 (2002) 612-613
44. Goldberg A.L. Functions of the proteasome: from protein degradation and immune surveillance to cancer therapy. Biochem. Soc. Trans. 35 (2007) 12-17
45. Gross A., McDonnell J.M., and Korsmeyer S.L. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13 (1999) 1899-1911
46. Guerrero S., Casanova I., Farre L., Mazo A., Capella G., and Mangues R. K-ras codon 12 mutation induces higher level of resistance to apoptosis and predisposition to anchorage-independent growth than codon 13 mutation or proto-oncogene overexpression. Cancer Res. 60 (2000) 6750-6756
47. Halliwell B. Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging 18 (2001) 685-716
48. Hara T., Nakamura K., Matsui M., et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441 (2006) 885-889
49. Harding H.P., Novoa I., Zhang Y., et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 6 (2000) 1099-1108
50. Harding H.P., Zhang Y., and Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397 (1999) 271-274
51. Hideshima T., Bradner J.E., Chauhan D., and Anderson K.C. Intracellular protein degradation and its therapeutic implications. Clin. Cancer Res. 11 (2005) 8530-8533
52. Hideshima T., Bradner J.E., Wong J., Chauhan D., Richardson P., Schreiber S.L., and Anderson K.C. Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc. Natl. Acad. Sci. USA 102 (2005) 8567-8572
53. Hideshima T., Chauhan D., Richardson P., et al. NF-kappa B as a therapeutic target in multiple myeloma. J. Biol. Chem. 277 (2002) 16639-16647
54. Hideshima T., Mitsiades C., Akiyama M., et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 101 (2003) 1530-1534
55. Hideshima T., Podar K., Chauhan D., et al. p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells. Oncogene 23 (2004) 8766-8776
56. Hideshima T., Richardson P., Chauhan D., et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 61 (2001) 3071-3076
57. Hosokawa N., Hirayoshi K., Nakai A., et al. Flavonoids inhibit the expression of heat shock proteins. Cell Struct. Funct. 15 (1990) 393-401
58. Hruban R.H., Goggins M., Parsons J., and Kern S.E. Progression model for pancreatic cancer. Clin. Cancer Res. 6 (2000) 2969-2972
59. Hruban R.H., Wilentz R.E., and Kern S.E. Genetic progression in the pancreatic ducts. Am. J. Pathol. 156 (2000) 1821-1825
60. Jacquemont C., and Taniguchi T. Proteasome function is required for DNA damage response and fanconi anemia pathway activation. Cancer Res. 67 (2007) 7395-7405
61. Jiang H.Y., and Wek R.C. Phosphorylation of the alpha-subunit of the eukaryotic initiation factor-2 (eIF2alpha) reduces protein synthesis and enhances apoptosis in response to proteasome inhibition. J. Biol. Chem. 280 (2005) 14189-14202
62. Johnston J.A., Ward C.L., and Kopito R.R. Aggresomes: a cellular response to misfolded proteins. J. Cell Biol. 143 (1998) 1883-1898
63. Kabuta T., Suzuki Y., and Wada K. Degradation of amyotrophic lateral sclerosis-linked mutant Cu,Zn-superoxide dismutase proteins by macroautophagy and the proteasome. J. Biol. Chem. 281 (2006) 30524-30533
64. Kalivendi S.V., Cunningham S., Kotamraju S., Joseph J., Hillard C.J., and Kalyanaraman B. Alpha-synuclein up-regulation and aggregation during MPP+-induced apoptosis in neuroblastoma cells: intermediacy of transferrin receptor iron and hydrogen peroxide. J. Biol. Chem. 279 (2004) 15240-15247
65. Kaluz S., Kaluzova M., and Stanbridge E.J. Proteasomal inhibition attenuates transcriptional activity of hypoxia-inducible factor 1 (HIF-1) via specific effect on the HIF-1alpha C-terminal activation domain. Mol. Cell Biol. 26 (2006) 5895-5907
66. Kaufman R.J. Orchestrating the unfolded protein response in health and disease. J. Clin. Invest. 110 (2002) 1389-1398
67. Kawaguchi Y., Kovacs J.J., McLaurin A., Vance J.M., Ito A., and Yao T.P. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115 (2003) 727-738
68. Keats J.J., Fonseca R., Chesi M., et al. Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell 12 (2007) 131-144
69. Keller J.N., Huang F.F., Zhu H., Yu J., Ho Y.S., and Kindy T.S. Oxidative stress-associated impairment of proteasome activity during ischemia-reperfusion injury. J. Cereb. Blood Flow Metab. 20 (2000) 1467-1473
70. Khanbolooki S., Nawrocki S.T., Arumugam T., et al. Nuclear factor-kappaB maintains TRAIL resistance in human pancreatic cancer cells. Mol. Cancer Ther. 5 (2006) 2251-2260
71. Kikuchi S., Shinpo K., Takeuchi M., Tsuji S., Yabe I., Niino M., and Tashiro K. Effect of geranylgeranylaceton on cellular damage induced by proteasome inhibition in cultured spinal neurons. J. Neurosci. Res. 69 (2002) 373-381
72. Kloetzel P.M., and Ossendorp F. Proteasome and peptidase function in MHC-class-I-mediated antigen presentation. Curr. Opin. Immunol. 16 (2004) 76-81
73. Komatsu M., Waguri S., Chiba T., et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441 (2006) 880-884
74. Komatsu M., Waguri S., Ueno T., et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169 (2005) 425-434
75. Kopito R.R. Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 10 (2000) 524-530
76. Kopito R.R., and Sitia R. Aggresomes and Russell bodies. Symptoms of cellular indigestion?. EMBO Rep. 1 (2000) 225-231
77. Kutuk O., and Letai A. Regulation of Bcl-2 family proteins by posttranslational modifications. Curr. Mol. Med. 8 (2008) 102-118
78. Landis-Piwowar K.R., Kilacic V., Chen D., et al. The proteasome as a potential target for novel anticancer drugs and chemosensitizers. Drug Resist. Updat. 9 (2006) 263-273
79. Lee A.H., Chu G.C., Iwakoshi N.N., and Glimcher L.H. XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands. EMBO J. 24 (2005) 4368-4380
80. Lee A.H., Iwakoshi N.N., Anderson K.C., and Glimcher L.H. Proteasome inhibitors disrupt the unfolded protein response in myeloma cells. Proc. Natl. Acad. Sci. USA 100 (2003) 9946-9951
81. Lee S.H., Soung Y.H., Lee J.W., et al. Mutational analysis of Noxa gene in human cancers. APMIS 111 (2003) 599-604
82. Letai A., Bassik M.C., Walensky L.D., Sorcinelli M.D., Weiler S., and Korsmeyer S.J. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2 (2002) 183-192
83. Levine B., and Yuan J. Autophagy in cell death: an innocent convict?. J. Clin. Invest. 115 (2005) 2679-2688
84. Lightcap E.S., McCormack T.A., Pien C.S., Chau V., Adams J., and Elliott P.J. Proteasome inhibition measurements: clinical application. Clin. Chem. 46 (2000) 673-683
85. Ling Y.H., Liebes L., Zou Y., and Perez-Soler R. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to bortezomib, a novel proteasome inhibitor, in human H460 non-small cell lung cancer cells. J. Biol. Chem. 278 (2003) 33714-33723
86. Liu C.Y., Schroder M., and Kaufman R.J. Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum. J. Biol. Chem. 275 (2000) 24881-24885
87. Liu C.Y., Wong H.N., Schauerte J.A., and Kaufman R.J. The protein kinase/endoribonuclease IRE1alpha that signals the unfolded protein response has a luminal N-terminal ligand-independent dimerization domain. J. Biol. Chem. 277 (2002) 18346-18356
88. Lowe S.W., Ruley H.E., Jacks T., and Housman D.E. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74 (1993) 957-967
89. Lü S., Yang J., and Song X. Point mutation of the proteasome β5 subunit gene is an important mechanism of bortezomib resistance in bortezomib-selected variant of Jurkat T cell lymphoblastic lymphoma/leukemia line. J. Pharmacol. Exp. Ther. 326 (2008) 423-431
90. Ma Y.Y., Wei S.J., Lin Y.C., et al. PIK3CA as an oncogene in cervical cancer. Oncogene 19 (2000) 2739-2744
91. Magagnin M.G., Koritzinsky M., and Wouters B.G. Patterns of tumor oxygenation and their influence on the cellular hypoxic response and hypoxia-directed therapies. Drug Resist. Updat. 9 (2006) 185-197
92. Mayo M.W., Wang C.Y., Cogswell P.C., Rogers-Graham K.S., Lowe S.W., Der C.J., and Baldwin Jr. A.S. Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras. Science 278 (1997) 1812-1815
93. McCullough K.D., Martindale J.L., Klotz L.O., Aw T.Y., and Holbrook N.J. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol. Cell Biol. 21 (2001) 1249-1259
94. Meister S., Schubert U., Neubert K., et al. Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition. Cancer Res. 67 (2007) 1783-1792
95. Mestre-Escorihuela C., Rubio-Moscardo F., Richter J.A., et al. Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas. Blood 109 (2007) 271-280
96. Miller C.P., Ban K., Dujka M.E., McConkey D.J., Munsell M., Palladino M., and Chandra J. NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells. Blood 110 (2007) 267-277
97. Miller, R.L., James-Kracke, M., Sun, G.Y., Sun, A.Y., in press. Oxidative and inflammatory pathways in Parkinson's disease. Neurochem. Res.
98. Mimnaugh E.G., Xu W., Vos M., et al. Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity. Mol. Cancer Ther. 3 (2004) 551-566
99. Mitsiades C.S., Mitsiades N., McMullan C.J., et al. Antimyeloma activity of heat shock protein-90 inhibition. Blood 107 (2006) 1092-1100
100. Mitsiades N., Mitsiades C.S., Poulaki V., et al. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc. Natl. Acad. Sci. USA 99 (2002) 14374-14379
101. Mizushima N., and Klionsky D.J. Protein turnover via autophagy: implications for metabolism. Annu. Rev. Nutr. 27 (2007) 19-40
102. Mizushima N., Levine B., Cuervo A.M., and Klionsky D.J. Autophagy fights disease through cellular self-digestion. Nature 451 (2008) 1069-1075
103. Moreau A.S., Jia X., Ngo H.T., et al. Ghobrial, protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia. Blood 109 (2007) 4964-4972
104. Moretti L., Yang E.S., Kim K.W., and Lu B. Autophagy signalling in cancer and its potential as a novel target to improve anticancer therapy. Drug Resist. Updat. 10 (2007) 135-143
105. Nawrocki S.T., Bruns C.J., Harbison M.T., et al. Effects of the proteasome inhibitor PS-341 on apoptosis and angiogenesis in orthotopic human pancreatic tumor xenografts. Mol. Cancer Ther. 1 (2002) 1243-1253
106. Nawrocki S.T., Carew J.S., Dunner Jr. K., Boise L.H., Chiao P.J., Huang P., Abbruzzese J.L., and McConkey D.J. Bortezomib inhibits PKR-like endoplasmic reticulum (ER) kinase and induces apoptosis via ER stress in human pancreatic cancer cells. Cancer Res. 65 (2005) 11510-11519
107. Nawrocki S.T., Carew J.S., Maclean K.H., et al. Myc regulates aggresome formation, the induction of Noxa, and apoptosis in response to the combination of bortezomib and SAHA. Blood 112 (2008) 2917-2926
108. Nawrocki S.T., Carew J.S., Pino M.S., et al. Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis. Cancer Res. 65 (2005) 11658-11666
109. Nawrocki S.T., Carew J.S., Pino M.S., et al. Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. Cancer Res. 66 (2006) 3773-3781
110. Nawrocki S.T., Sweeney-Gotsch B., Takamori R., and McConkey D.J. The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts. Mol. Cancer Ther. 3 (2004) 59-70
111. Nerini-Molteni S., Ferrarini M., Cozza S., Caligaris-Cappio F., and Sitia R. Redox homeostasis modulates the sensitivity of myeloma cells to bortezomib. Br. J. Haematol. 141 (2008) 494-503
112. Nguyen M., Marcellus R.C., Roulston A., et al. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc. Natl. Acad. Sci. USA 104 (2007) 19512-19517
113. Nickeleit I., Zender F., Sasse F., et al. Argyrin A reveals a critical role for the tumor suppressor protein p27kip1 in mediating anti-tumor activities in response to proteasome inhibition. Cancer Cell 14 (2008) 23-35
114. Nikiforov M.A., Riblett M., Tang W.H., et al. Tumor cell-selective regulation of NOXA by c-MYC in response to proteasome inhibition. Proc. Natl. Acad. Sci. USA 104 (2007) 19488-19493
115. Nikrad M., Johnson T., Puthalalath H., Coultas L., Adams J., and Kraft A.S. The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim. Mol. Cancer Ther. 4 (2005) 443-449
116. Obeng E.A., Carlson L.M., Gutman D.M., Harrington Jr. W.J., Lee K.P., and Boise L.H. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood 107 (2006) 4907-4916
117. ® resistance: proteasome subunit β5 (PSMB5) gene mutation and overexpression of PSMB5 protein. Blood 112 (2008) 2489-2499
118. Ogino S., Kawasaki T., Ogawa A., Kirkner G.J., Loda M., and Fuchs C.S. Cytoplasmic localization of p27 (cyclin-dependent kinase inhibitor 1B/KIP1) in colorectal cancer: inverse correlations with nuclear p27 loss, microsatellite instability, and CpG island methylator phenotype. Hum. Pathol. 38 (2007) 585-592
119. Oltersdorf T., Elmore S.W., Shoemaker A.R., et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435 (2005) 677-681
120. Osaki M., Oshimura M., and Ito H. PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9 (2004) 667-676
121. Oyadomari S., Koizumi A., Takeda K., et al. Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. J. Clin. Invest. 109 (2002) 525-532
122. Pandey U.B., Nie Z., Batlevi Y., et al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447 (2007) 859-863
123. Paoluzzi L., Gonen M., Bhagat G., et al. The BH3-only mimetic ABT-737 synergizes the anti-neoplastic activity of proteasome inhibitors in lymphoid malignancies. Blood 112 (2008) 2906-2916
124. Papandreou C.N., Daliani D.D., Nix D., et al. Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J. Clin. Oncol. 22 (2004) 2108-2121
125. Papandreou C.N., and Logothetis C.J. Bortezomib as a potential treatment for prostate cancer. Cancer Res. 64 (2004) 5036-5043
126. Podar K., Gouill S.L., Zhang J., et al. A pivotal role for Mcl-1 in Bortezomib-induced apoptosis. Oncogene 27 (2008) 721-731
127. Puthalakath H., Huang D.C., O'Reilly L.A., King S.M., and Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cell 3 (1999) 287-296
128. Qin J.Z., Xin H., Sitailo L.A., Denning M.F., and Nickoloff B.J. Enhanced killing of melanoma cells by simultaneously targeting Mcl-1 and NOXA. Cancer Res. 66 (2006) 9636-9645
129. Qin J.Z., Ziffra J., Stennett L., et al. Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Cancer Res. 65 (2005) 6282-6293
130. Reimold A.M., Etkin A., Clauss I., et al. An essential role in liver development for transcription factor XBP-1. Genes Dev. 14 (2000) 152-157
131. Reimold A.M., Iwakoshi N.N., and Manis J. Plasma cell differentiation requires the transcription factor XBP-1. Nature 412 (2001) 300-307
132. Richardson P.G., Barlogie B., Berenson J., et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. New Engl. J. Med. 348 (2003) 2609-2617
133. Richardson P.G., Sonneveld P., Schuster M.W., et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. New Engl. J. Med. 352 (2005) 2487-2498
134. Ron D. Translational control in the endoplasmic reticulum stress response. J. Clin. Invest. 110 (2002) 1383-1388
135. Ruiz S., Krupnik Y., Keating M., Chandra J., Palladino M.A., and McConkey D.J. The proteasome inhibitor NPI-0052 is a more effective inducer of apoptosis than bortezomib in lymphocytes from patients with chronic lymphocytic leukemia (CLL). Mol. Cancer Ther. 5 (2006) 1836-1843
136. Russo S.M., Tepper J.E., Baldwin Jr. A.S., et al. Enhancement of radiosensitivity by proteasome inhibition: implications for a role of NF-kappaB. Int. J. Radiat. Oncol. Biol. Phys. 50 (2001) 183-193
137. Scheuner D., Song B., McEwen E., et al. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol. Cell 7 (2001) 1165-1176
138. Shen J., Chen X., Hendershot L., and Prywes R. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev. Cell 3 (2002) 99-111
139. Shi Y., Vattem K.M., Sood R., An J., Liang J., Stramm L., and Wek R.C. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol. Cell Biol. 18 (1998) 7499-7509
140. Shi Y., Yan H., Frost P., Gera J., and Lichtenstein A. Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade. Mol. Cancer Ther. 4 (2005) 1533-1540
141. Shi Y.Y., Small G.W., and Orlowski R.Z. Proteasome inhibitors induce a p38 mitogen-activated protein kinase (MAPK)-dependent anti-apoptotic program involving MAPK phosphatase-1 and Akt in models of breast cancer. Breast Cancer Res. Treat. 100 (2006) 33-47
142. Shin D.H., Chun Y.S., Lee D.S., Huang L.E., and Park J.W. Bortezomib inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated repression of hypoxia-inducible factor-1. Blood 111 (2008) 3131-3136
143. Shin I., Yakes F.M., Rojo F., Shin N.Y., Bakin A.V., Baselga J., and Arteaga C.L. PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat. Med. 8 (2002) 1145-1152
144. Shrader M., Pino M.S., Lashinger L., Bar-Eli M., Adam L., Dinney C.P., and McConkey D.J. Gefitinib reverses TRAIL resistance in human bladder cancer cell lines via inhibition of AKT-mediated X-linked inhibitor of apoptosis protein expression. Cancer Res. 67 (2007) 1430-1435
145. Shringarpure R., Catley L., Bhole D., et al. Gene expression analysis of B-lymphoma cells resistant and sensitive to bortezomib. Br. J. Haematol. 134 (2006) 145-156
146. Talloczy Z., Jiang W., Virgin IV H.W., et al. Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway. Proc. Natl. Acad. Sci. USA 99 (2002) 190-195
147. Tan T.T., Degenhardt K., Nelson D.A., et al. Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy. Cancer Cell 7 (2005) 227-238
148. Thompson J.E., and Thompson C.B. Putting the rap on Akt. J. Clin. Oncol. 22 (2004) 4217-4226
149. Traenckner E.B., Wilk S., and Baeuerle P.A. A proteasome inhibitor prevents activation of NF-kappa B and stabilizes a newly phosphorylated form of I kappa B-alpha that is still bound to NF-kappa B. EMBO J. 13 (1994) 5433-5441
150. Travers K.J., Patil C.K., Wodicka L., Lockhart D.J., Weissman J.S., and Walter P. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101 (2000) 249-258
151. Twombly R. First proteasome inhibitor approved for multiple myeloma. J. Natl. Cancer Inst. 95 (2003) 845
152. Uehara T., Nakamura T., Yao D., et al. S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature 441 (2006) 513-517
153. Urushitani M., Kurisu J., Tsukita K., and Takahashi R. Proteasomal inhibition by misfolded mutant superoxide dismutase 1 induces selective motor neuron death in familial amyotrophic lateral sclerosis. J. Neurochem. 83 (2002) 1030-1042
154. Van Antwerp D.J., Martin S.J., Kafri T., Green D.R., and Verma I.M. Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science 274 (1996) 787-789
155. Varfolomeev E., Blankenship J.W., Wayson S.M., et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell 131 (2007) 669-681
156. Vaziri S.A., Hill J., Chikamori K., et al. Sensitization of DNA damage-induced apoptosis by the proteasome inhibitor PS-341 is p53 dependent and involves target proteins 14-3-3sigma and survivin. Mol. Cancer Ther. 4 (2005) 1880-1890
157. Voorhees P.M., Dees E.C., O'Neil B., and Orlowski R.Z. The proteasome as a target for cancer therapy. Clin. Cancer Res. 9 (2003) 6316-6325
158. Vousden K.H., and Lane D.P. p53 in health and disease. Nat. Rev. Mol. Cell Biol. 8 (2007) 275-283
159. Wang C.Y., Mayo M.W., and Baldwin Jr. A.S. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science 274 (1996) 784-787
160. Wang W., Abbruzzese J.L., Evans D.B., Larry L., Cleary K.R., and Chiao P.J. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin. Cancer Res. 5 (1999) 119-127
161. Wang Z., Zhang B., Yang L., Ding J., and Ding H.F. Constitutive production of NF-kappaB2 p52 is not tumorigenic but predisposes mice to inflammatory autoimmune disease by repressing Bim expression. J. Biol. Chem. 283 (2008) 10698-10706
162. Wei M.C., Zong W.X., Cheng E.H., et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292 (2001) 727-730
163. Williams S., Pettaway C., Song R., Papandreou C., Logothetis C., and McConkey D.J. Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumor xenografts. Mol. Cancer Ther. 2 (2003) 835-843
164. Williams S.A., and McConkey D.J. The proteasome inhibitor bortezomib stabilizes a novel active form of p53 in human LNCaP-Pro5 prostate cancer cells. Cancer Res. 63 (2003) 7338-7344
165. Workman P., Burrows F., Neckers L., and Rosen N. Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann. N. Y. Acad. Sci. 1113 (2007) 202-216
166. Worm J., Bartkova J., Kirkin A.F., Straten P., Zeuthen J., Bartek J., and Guldberg P. Aberrant p27Kip1 promoter methylation in malignant melanoma. Oncogene 19 (2000) 5111-5115
167. Wu M., Lee H., Bellas R.E., et al. Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells. EMBO J. 15 (1996) 4682-4690
168. Xiao C., Srinivasan L., Calado D.P., et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat. Immunol. 9 (2008) 405-414
169. Yamashita M., Kuwahara M., Suzuki A., et al. Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene. J. Exp. Med. 205 (2008) 1109-1120
170. Yang G., Ayala G., De Marzo A., et al. Elevated Skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival. Clin. Cancer Res. 8 (2002) 3419-3426
171. Yang H., Zhou H.Y., Li B., Niu G.Z., and Chen S.D. Downregulation of parkin damages antioxidant defenses and enhances proteasome inhibition-induced toxicity in PC12 cells. J. Neuroimmune Pharmacol. 2 (2007) 276-283
172. Yang W., Monroe J., Zhang Y., George D., Bremer E., and Li H. Proteasome inhibition induces both pro- and anti-cell death pathways in prostate cancer cells. Cancer Lett. 243 (2006) 217-227
173. Yerlikaya A., Kimball S.R., and Stanley B.A. Phosphorylation of eIF2alpha in response to 26S proteasome inhibition is mediated by the haem-regulated inhibitor (HRI) kinase. Biochem. J. 412 (2008) 579-588
174. Yu C., Friday B.B., Lai J.P., et al. Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways. Mol. Cancer Ther. 5 (2006) 2378-2387
175. Yu C., Rahmani M., Conrad D., Subler M., Dent P., and Grant S. The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571. Blood 102 (2003) 3765-3774
176. Yu J., Tiwari S., Steiner P., and Zhang L. Differential apoptotic response to the proteasome inhibitor bortezomib [VELCADE, PS-341] in Bax-deficient and p21-deficient colon cancer cells. Cancer Biol. Ther. 2 (2003) 694-699
177. Zhang P., McGrath B., Li S., et al. The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Mol. Cell Biol. 22 (2002) 3864-3874
178. Zhang L., Ming L., and Yu L. BH3 mimetics to improve cancer therapy: mechanisms and examples. Drug Resist. Updat. 10 (2007) 207-217
179. Zhu H., Zhang L., Dong F., et al. Bik/NBK accumulation correlates with apoptosis-induction by bortezomib (PS-341, Velcade) and other proteasome inhibitors. Oncogene 24 (2005) 4993-4999
180. Zinszner H., Kuroda M., Wang X., et al. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 12 (1998) 982-995
181. Zou W., Yue P., Lin N., et al. Vitamin C inactivates the proteasome inhibitor PS-341 in human cancer cells. Clin. Cancer Res. 12 (2006) 273-280