Proteasome inhibitors: From research tools to drug candidates

Chemistry and Biology

Volumn 8, Issue 8, 2001, Pages 739-758

  Kisselev, A F ^a   Goldberg, A L ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Drug candidate; Proteasome inhibitor; Ubiquitin proteasome pathway

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ANTIINFLAMMATORY AGENT; ANTINEOPLASTIC AGENT; ATP DEPENDENT 26S PROTEASE; MULTIENZYME COMPLEX; PEPTIDE HYDROLASE; PROTEASOME; PROTEIN SUBUNIT; PROTEINASE INHIBITOR; UBIQUITIN;

ANIMAL; BINDING SITE; CATALYSIS; CHEMICAL STRUCTURE; CHEMISTRY; CLASSIFICATION; HUMAN; METABOLISM; NON-PROGRAMMATIC; PROTEIN QUATERNARY STRUCTURE; REVIEW;

NON-PROGRAMMATIC;

ANIMALS; ANTI-HIV AGENTS; ANTI-INFLAMMATORY AGENTS; ANTINEOPLASTIC AGENTS; BINDING SITES; CATALYSIS; HUMANS; MODELS, MOLECULAR; MULTIENZYME COMPLEXES; PEPTIDE HYDROLASES; PROTEASE INHIBITORS; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN STRUCTURE, QUATERNARY; PROTEIN SUBUNITS; UBIQUITIN;

EID: 0034864799     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1074-5521(01)00056-4     Document Type: Review

References (152)

1. Lessons from the discovery of the ubiquitin system
2. A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes
3. Involvement of the proteasome in various degradative processes in mammalian cells
4. The ubiquitin-proteasome proteolytic pathway
5. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class 1 molecules
6. Lactacystin and clasto-lactacystin β-lactone modify multiple proteasome β-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation
7. How the cyclin became a cyclin: Regulated proteolysis in the cell cycle
8. The ubiquitin system
9. Ubiquitin-mediated degradation of active Src tyrosine kinase
10. Activation of protein kinase C triggers its ubiquitination and degradation
11. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27
12. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity
13. Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis
14. Degradation of cell proteins and generation of MHC class I-presented peptides
15. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway
16. Role of 26S proteasome and Hrd genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein
17. Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination
18. Peptides accelerate their uptake by activating a ubiquitin-dependent proteolytic pathway
19. Ubiquitin-mediated proteolysis in learning and memory
20. A role for the proteasome in the light response of the timeless clock protein
21. Targeted destabilization of HY5 during light-regulated development of Arabidopsis
22. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes
23. 2+-free calmodulin and calmodulin damaged by in vitro aging are selectively degraded by 26S proteasomes without ubiquitination
24. Multiple proteolytic systems, including the proteasome, contribute to CFTR processing
25. Degradation of CFTR by the ubiquitin-proteasome pathway
26. Degradation of a mutant secretory protein, alpha1-antitrypsin Z, in the endoplasmic reticulum requires proteasome activity
27. The 26S proteasome: A molecular machine designed for controlled proteolysis
28. The regulatory complex of Drosophila melanogaster 26S proteasomes: Subunit composition and localization of a deubiquitylating enzyme
29. Structure and functions of the 20S and 26S proteasomes
30. In vivo assembly of the proteasomal complexes, implications for antigen processing
31. Hybrid proteasomes. Induction by interferon-gamma and contribution to ATP-dependent proteolysis
32. The proteasome activator 11 S REG (PA28) and class I antigen presentation
33. The ATP dependence of the degradation of short- and long-lived proteins in growing fibroblasts
34. The proteasome: Paradigm of a self-compartmentalizing protease
35. Structure of 20S proteasome from yeast at 2.4 Å resolution
36. Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 Å resolution
37. A gated channel into the proteasome core particle
38. Conformational constraints in protein degradation by the 20S proteasome
39. A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3
40. The axial channel of the proteasome core particle is gated by the Rpt2 ATPase and controls both substrate entry and product release
41. Proteasomes in prokaryotes
42. An archaebacterial ATPase, homologous to ATPases in the eukaryotic 26 S proteasome, activates protein breakdown by 20 S proteasomes
43. Biochemical and physical properties of the Methanococcus jannaschii 20S proteasome and PAN, a homolog of the ATPase (Rpt) subunits of the eucaryal 26S proteasome
44. PAN, the proteasome activating nucleotidase from archaebacteria, is a molecular chaperone which unfolds protein substrate
45. Processive degradation of proteins and other catalytic properties of the proteasome from Thermoplasma acidophilum
46. The sizes of peptides generated from protein by mammalian 26S and 20S proteasomes: Implications for understanding the degradative mechanism and antigen presentation
47. Cleavage motifs of the yeast 20S proteasome beta subunits deduced from digests of enolase 1
48. Contribution of proteasomal beta-subunits to the cleavage of peptide substrates analyzed with yeast mutants
49. The multicatalytic proteinase complex, a major extralysosomal proteolytic system
50. Proteasome active sites allosterically regulate each other, suggesting a cyclical bite-chew mechanism for protein breakdown
51. Caspases: Enemies within
52. Evidence for the presence of five distinct proteolytic components in the pituitary multicatalytic proteinase complex. Properties of two components cleaving bonds on the carboxyl side of branched chain and small neutral amino acids
53. Components of the bovine pituitary multicatalytic proteinase complex (proteasome) cleaving bonds after hydrophobic residues
54. Kinetic studies of the branched chain amino acid preferring peptidase activity of the 20S proteasome: Development of a continious assay and inhibition by tripeptide aldehydes and clasto-lactacystin β-lactone
55. Cleavage of Pro-X and Glu-X bonds catalyzed by the branched chain amino acid preferring activity of the bovine pituitary multicatalytic proteinase complex (20S proteasome)
56. Evidence for the existence of a non-catalytic modifier site of peptide hydrolysis by the 20S proteasome
57. Lack of proteasome active site allostery as revealed by subunit-specific inhibitors
58. HslV-HslU - A novel ATP-dependent protease complex in Escherichia coli related to the eukaryotic proteasome
59. A protein catalytic framework with an N-terminal nucleophile is capable of self-activation
60. Proteasome from Thermoplasma acidophilum - A threonine protease
61. Inhibition of proteolytic enzymes
62. Why does threonine, and not serine, function as the active site nucleophile in proteasomes?
63. 14C]-3,4-dichloroisocoumarin with subunits of pituitary and spleen multicatalytic proteinase complexes (proteasomes)
64. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin
65. Covalent modification of the active site Thr of proteasome beta-subunits and the E. coli homologue HslV by a new class of inhibitors
66. Autocatalytic subunit processing couples active site formation in the 20S proteasome to completion of assembly
67. The active sites of the eukaryotic 20S proteasome and their involvement in subunit precursor processing
68. Identification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation
69. Emerging roles for cysteine proteases in human biology
70. Inhibition of the chymotrypsin-like activity of the pituitary multicatalytic proteinase complex
71. Selective inhibitors of the proteasome-dependent and vacuolar pathways of protein degradation in Saccharomyces cerevisiae
72. Calpain inhibition: An overview of its therapeutic potential
73. Potent and selective inhibitors of the proteasome: Dipeptidyl boronic acids
74. Novel dipeptide aldehydes are proteasome inhibitors and block the MHC-I antigen-processing pathway
75. The ubiquitin-proteasome pathway is required for processing the NF-kappa-B1 precursor protein and the activation of NF-kappa-B
76. Differential inhibition of calpain and proteasome activities by peptidyl aldehydes of di-leucine and tri-leucine
77. A new inhibitor of the chymotrypsin-like activity of the multicatalytic proteinase complex (20S proteasome) induces accumulation of ubiquitin-protein conjugates in a neuronal cell
78. 14-3-3s regulate global cleavage of their diverse binding partners in sugar-starved Arabidopsis cells
79. Proteasome inhibitors: A novel class of potent and effective antitumor agents
80. Active site-directed inhibitors of Rhodococcus 20S proteasome. Kinetics and mechanism
81. Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells
82. Total synthesis and biological activity of lactacystin, omuralide and analogs
83. Mechanistic studies on the inactivation of the proteasome by lactacystin - A central role for clasto-lactacystin β-lactone
84. Mechanistic studies on the inactivation of the proteasome by lactacystin in cultured cells
85. Lactacystin, a specific inhibitor of the proteasome, inhibits human platelet lysosomal cathepsin A-like enzyme
86. A giant protease with potential to substitute for some functions of the proteasome
87. Vinyl sulfones as mechanism-based cysteine protease inhibitors
88. Substrate binding and sequence preference of the proteasome revealed by active-site-directed affinity probes
89. Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase activity
90. Global analysis of proteasomal substrate specificity using positional-scanning libraries of covalent inhibitors
91. Extended-peptide based inhibitors efficiently target the proteasome and reveal overlapping specificities of catalytic subunits
92. Eponemycin exerts its autitumor effect through the inhibition of proteasome function
93. Crystal structure of epoxomicin: 20S proteasome reveals a molecular basis for selectivity of alpha′,beta′-epoxyketone proteasome inhibitors
94. Inhibitors of the chymotrypsin-like activity of proteasome based on di- and tri-peptidyl alpha-keto aldehydes (glyoxals)
95. P′-extended α-ketoamide inhibitors of proteasome
96. A new structural class of proteasome inhibitors that prevent NF-kappa B activation
97. Bivalency as a principle for proteasome inhibition
98. TMC-95A, B, C, and D, novel proteasome inhibitors produced by Apiospora montagnei Sacc. TC 1093 - Taxonomy, production, isolation, and biological activities
99. Crystal structure of the 20S proteasome:TMC-95A complex: A non-covalent proteasome inhibitor
100. The secondary fungal metabolite gliotoxin targets proteolytic activities of the proteasome
101. Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo
102. How an inhibitor of the HIV-I protease modulates proteasome activity
103. Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase
104. The antitumor drug aclacinomycin A, which inhibits the degradation of ubiquitinated proteins, shows selectivity for the chymotrypsin-like activity of the bovine pituitary 20S proteasome
105. Cyclosporine A is an uncompetitive inhibitor of proteasome activity and prevents NF-κB activation
106. Inhibition of the proteolytic activity of the multicatalytic proteinase complex (proteasome) by substrate-related peptidyl aldehydes
107. Proteasome inhibition leads to a heat-shock response, induction of endoplasmic reticulum chaperones, and thermotolerance
108. Proteasome inhibitors cause induction of heat shock proteins and trehalose, which together confer thermotolerance in Saccharomyces cerevisiae
109. Proteasome inhibitor induced gene expression profiles reveal overexpression of transcriptional regulators ATF3, GADD153 and MAD1
110. Protease inhibitor-induced apoptosis: Accumulation of wt p53, p21(WAF1/CIP1) and induction of apoptosis are independent markers of proteasome inhibition
111. Induction of G1 arrest and selective growth inhibition by lactacystin in human umbilical vein endothelial cells
112. Activation of the cell death program by inhibition of proteasome function
113. Inhibition of proteasome function induces programmed cell death in proliferating endothelial cells
114. Tumor growth inhibition induced in a murine model of human Burkitt's lymphoma by a proteasome inhibitor
115. Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent kinase inhibitor p27 and induce apoptosis in transformed, but not normal, human fibroblasts
116. Increased sensitivity of CLL-derived lymphocytes to apoptotic death activation by the proteasome-specific inhibitor lactacystin
117. p53-dependent induction of apoptosis by proteasome inhibitors
118. Proteasome inhibitors activate stress kinases and induce Hsp72. Diverse effects on apoptosis
119. Proteasome inhibition in neuronal cells induces a proinflammatory response manifested by upregulation of cyclooxygenase-2, its accumulation as ubiquitin conjugates, and production of the prostaglandin PGE(2)
120. Detailed analysis of cell cycle kinetics upon proteasome inhibition
121. P53-dependent cell cycle arrest induced by N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal in platelet-derived growth factor-stimulated human fibroblasts
122. Role of proteasomes in T cell activation and proliferation
123. Bax degradation by the ubiquitin/proteasome-dependent pathway: Involvement in tumor survival and progression
124. Inhibition of TNF-induced apoptosis by NF-kappa B
125. Cells adapted to the proteasome inhibitor 4-hydroxy-5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival
126. Proteasomes play an essential role in thymocyte apoptosis
127. Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons
128. Inhibition of etoposide-induced apoptosis with peptide aldehyde inhibitors of proteasome
129. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli
130. Dephosphorylation targets Bcl-2 for ubiquitin-dependent degradation: A link between the apoptosome and the proteasome pathway
131. The proteasome is involved in angiogenesis
132. The proteasome inhibitor PS-341 in cancer therapy
133. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells
134. New agents in cancer clinical trials
135. A proteolytic system that compensates for loss of proteasome function
136. C-myc overexpression activates alternative pathways for intracellular proteolysis in lymphoma cells
137. Two new proteases in the MHC class I processing pathway
138. Activators and target genes of Rel/NF-kappaB transcription factors
139. Inhibition of NF-kappa B activation in vitro and in vivo: Role of 26S proteasome
140. A novel and efficient synthesis of a highly active analogue of clasto-lactacystin beta-lactone
141. Proteasome inhibition: A novel mechanism to combat asthma
142. Cardioprotective effects of a novel proteasome inhibitor following ischemia and reperfusion in the isolated perfused rat heart
143. Proteasome inhibitor PS519 reduces infarction and attenuates leukocyte infiltration in a rat model of focal cerebral ischemia
144. Ubiquitin in retrovirus assembly: Actor or bystander
145. Proteasome inhibition interferes with Gag polyprotein processing, release, and maturation of HIV-1 and HIV-2
146. The selective proteasome inhibitors lactacystin and epoxomicin can be used to either up- or down-regulate antigen presentation at nontoxic doses
147. 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide
148. Towards subunit-specific proteasome inhibitors: Synthesis and evaluation of peptide alpha′,beta′-epoxyketones
149. Bifunctional inhibitors of the trypsin-like activity of eukaryotic proteasomes
150. Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells
151. A ubiquitin-based tagging system for controlled modulation of protein stability
152. Structural basis for the activation of 20S proteasomes by 11S regulators