Ubiquitins, proteasomes, sumoylation and application today and in future for cancer and other diseases therapy I. Ubiquitin-proteasome system and the transcription factor NF-κB
Authors:
O. Fuchs 1; R. Neuwirtová 2
Authors‘ workplace:
Ústav hematologie a krevní transfuze, Praha, ředitel prof. MUDr. Pavel Klener, DrSc.
1; I. interní klinika 1. lékařské fakulty UK a VFN, Praha, přednosta prof. MUDr. Pavel Klener, DrSc.
2
Published in:
Vnitř Lék 2006; 52(4): 371-378
Category:
Review
Overview
Proteasome is protein complex with proteolytic activity. Proteasomes are in addition to lysosomes the main proteolytic machinery of the eukaryotic cell. Proteins destined for degradation in proteasomes are marked by ubiquitinylation, which consists in attachment of polyubiquitin to relevant protein. The transport of polyubiquitinylated protein follows to proteasome, where protein is cleaved into small peptides. Besides polyubiquitin attachment to protein, monoubiquitinylation of proteins exists and has an important role in DNA repair, transcription of genes, endocytosis and signal transduction. The function of an important transcription factor NF-κB is connected with proteasome. NF-κB is activated after the proteolysis of its inhibitor IκB in proteasome. Ubiqutinylation and degradation of protein in proteasome and the activation of NF-κB play significant roles in taking proteins away and in expression of great numbers of genes important for the regulation of the cell cycle and apoptosis of cells. The inhibition of proteasomes has antiproliferative and antiinflammatory effects and opens new therapeutic approaches to a treatment of cancer and some inflammatory diseases. We divided the review into three parts: I. Ubiquitin-proteasome system and the transcription factor NF-κB, II. Sumoylation and neddylation as post-translational modification of proteins similar to ubiquitinylation and their significance and lastly III. Using of the knowledge of ubiquitin-proteasome system in cancer and other diseases therapy.
Key words:
ubiquitin - proteasome - transcription factor NF-κB
Sources
1. Harris JR. Release of a macromolecular protein component from human erythrocyte ghosts. Biochim Biophys Acta 1968; 150: 534-537.
2. Arrigo AP, Tanaka K., Goldberg AL et al. Identity of the 19 S „prosome“ particle with the large multifunctional protease complex of mammalian cells (the proteasome). Nature 1988; 331: 192-194.
3. Zwickl P, Lottspeich F, Dahlmann B et al. Cloning and sequencing of the gene encoding the large (alpha-) subunit of the proteasome from Thermoplasma acidophilium. FEBS Lett 1991; 278: 217-221.
4. Goldstein G, Scheid M, Hammerling U et al. Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc Natl Acad Sci USA 1975; 72: 11-15.
5. Hershko A, Ciechanover A, Heller H et al. Proposed role of ATP in protein breakdown: conjugation of proteins with multiple chains of the polypeptide of ATP- dependent proteolysis. Proc Natl Acad Sci USA 1980; 77: 1783-1786.
6. Hershko A, Heller H, Elias S et al. Components of ubiquitin-protein ligase system. J Biol Chem 1983; 258: 8206-8214.
7. Hershko A, Heller H, Eytan E et al. ATP-dependent degradation of ubiquitin-protein conjugates. Proc Natl Acad Sci USA 1984; 81: 1619-1623.
8. Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998; 67: 425-479.
9. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 2002; 82: 373-428.
10. Baker RT, Board PG. The human ubiquitin gene family: structure of a gene and pseudogenes from the Ub B subfamily. Nucleic Acids Res 1987; 15: 443-463.
11. Baker RT, Board PG. The human ubiquitin-52 amino acid fusion protein gene shares several structural features with mammalian ribosomal protein genes. Nucleic Acids Res 1991; 19: 1035-1040.
12. Adams J. Potential for proteasome inhibition in the treatment of cancer. Drug Discovery Today 2003; 8: 307-315.
13. Pickart CM, Eddins MJ. Ubiquitin: structures, functions, mechanisms. Biochim Biophys Acta 2004; 1695: 55-72.
14. Ciechanover A. Proteolzsis: from the lzsosome to ubiquitin and the proteasome. Nature Rev Mol Cell Biol 2005; 6: 79-87.
15. Hoppe T. Multiubiquitylation by E4 enzymes: “one size” doesn´t fit all. Trends Biochem Sci 2005; 30: 183-187.
16. Pickart CM. Ubiquitin in chains. Trends Biochem Sci 2000; 25: 544-548.
17. Wilkinson KD. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J 1997; 11: 1245-1256.
18. D´Andrea A, Pellman D. Deubiquitinating enzymes: a new class of biological regulators. Crit Rev Biochem Mol Biol 1998; 33: 332-337.
19. Wilkinson KD. Ubiquitination and deubiquitination: targeting of proteins for degradation by the proteasome. Semin Cell Dev Biol 2000; 11: 141-148.
20. Wong BR, Parlati F, Qu K et al. Drug discovery in the ubiquitin regulatory pathway. Drug Discov Today 2003; 8: 746-754.
21. Bachmair A, Finley DJ, Varshavsky A. In vivo half-life of a protein is a function of its amino-terminal residue. Science 1986; 234: 179-186.
22. Bachmair A, Varshavsky A. The degradation signal in a short-lived protein. Cell 1989; 56: 1019-1032.
23. Chau V, Tobias JW, Bachmair A et al. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 1989; 243: 1576-1583.
24. Johnson ES, Gonda DK, Varshavsky A. Cis-trans recognition and subunit-specific degradation of short-lived proteins. Nature 1990; 346: 287-291.
25. Bartel B, Wünning I, Varshavsky A. The recognition component of the N-end rule pathway. EMBO J 1990; 9: 3179-3189.
26. Varshavsky A, Turner G, Du F et al. The ubiquitin system and the N-end rule pathway. Biol Chem 2000; 381: 779-789.
27. Rao H, Uhlmann F, Nasmyth K et al. Degradation of cohesin subunit and the N-end rule pathway is essential for chromosome stability. Nature 2000; 410: 955-959.
28. Jaakkola P, Mole DR, Tian YM et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 2001; 292: 468-472.
29. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-B activity. Annu Rev Immunol 2000; 18: 621-663.
30. Amati B. Myc degradation: dancing with ubiquitin ligases. Proc Natl Acad Sci USA 2004; 101: 8843-8844.
31. Ashcroft M, Taya Y, Vousden KH. Stress signals utilize multiple pathways to stabilize p53. Mol Cell Biol 2000; 20: 3224-3233.
32. Barnes PJ, Karin M. Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997; 336: 1066-1071.
33. Yaron A, Hatzubai A, Davis M et al. Identification of the receptor component of the IB-ubiquitin ligase. Nature 1998; 396: 590-594.
34. Yaron A, Gonen H, Alkalay I et al. Inhibition of NF-B cellular function via specific targeting of the IB-ubiquitin ligase. EMBO J 1997; 16: 6486-6494.
35. Chen ZJ. Ubiquitin signalling in the NF-B pathway. Nature Cell Biol 2005; 7: 758-765.
36. Yamamoto Y, Gaynor RB. IκB kinases: key regulators of the NF-κB pathway. Trends Biochem Sci 2004; 29: 72-79.
37. Leníček M, Muchová L, Vítek L. Nukleární faktor κB v léčbě zánětlivých a nádorových onemocnění. Čas Lék Čes 2004; 143: 680-684.
38. Fribley A, Zeng Q, Wang CY. 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 2004; 24: 9695-9704.
39. Nawrocki ST, Carew JS, Dunner K et al. Bortezomib inhibits PKR-like endoplasmic reticulum (ER) kinase and induces apoptosis via ER stress in human pancreatic cancer cancer cells. Cancer Res 2005; 65: 11510-11519.
40. 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 2005; 24: 4993-4999.
41. Nikrad M, Johnson T, Puthalalath H et al. The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim. Mol Cancer Ther 2005; 4: 443-449.
42. Qin JZ, Ziffra J, Stennett L et al. Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Cancer Res 2005; 65: 6282-6293.
43. Pérez-Galán P, Roué G, Villamor N et al. The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status. Blood 2006; 107: 257-264.
44. Johnson ES. Ubiquitin branches out. Nat Cell Biol 2002; 4: E295-E298.
45. Schnell JD, Hicke L. Non-traditional functions of ubiquitin and ubiquitin-binding proteins. J Biol Chem 2003; 278: 35857-35860.
46. Sun L, Chen ZJ. The novel functions of ubiquitination in signaling. Curr Opin Cell Biol 2004; 16: 119-126.
47. Pickart CM. Mechanisms underlying ubiquitination. Annu Rev Biochem 2001; 70: 503-533.
48. Weissman AM. Themes and variations on ubiquitylation. Nat Rev Mol Cell Biol 2001; 2: 169-178.
49. Aguilar RC, Wendland B. Endocytosis of membrane receptors: Two pathways are better than one. Proc Natl Acad Sci USA 2005; 102: 2679-2680.
50. Sigismund S, Woelk T, Puri C et al. Clathrin-independent endocytosis of ubiquitinated cargos. Proc Natl Acad Sci USA 2005; 102: 2760-2765.
51. D’Andrea AD. The Fanconi road to cancer. Genes Dev 2003; 17: 1933-1936.
52. Montes de Oca R, Andreassen PR, Margossian SP et al. Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin. Blood 2005; 105: 1003-1009.
53. Zhang Y. Transcriptional regulation by histone ubiquitination and deubiquitination. Genes Dev 2003; 17: 2733-2740.
54. Zhu B, Zheng Y, Pham AD et al. Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol Cell 2005; 20: 601-611.
55. Zhang Y, Reinberg D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev 2001; 15: 2343-2360.
56. Zhang K, Dent SYR. Histone modifying enzymes and cancer: going beyond histones. J Cell Biochem 2005; 96: 1137-1148.
57. Deng L, Wang C, Spencer E et al. Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 2000; 103: 351-361.
58. Wojcik C, DeMartino GN. Intracellular localization of proteasomes. Int J Biochem Cell Biol 2003; 35: 579-589.
59. Fuchs O. Proteazomy. Biol Listy 1996; 61: 13-27.
60. Špička I, Kleibl Z, Hájek R. Bortezomibum. Remedia 2005; 15: 196-203.
61. Groll M, Huber R. Substrate access and processing by the 20S proteasome core particle. Int J Biochem Cell Biol 2003; 35: 606-616.
62. Pickart CM, Cohen RE. Proteasomes and their kin: proteases in the machine age. Nat Rev Mol Cell Biol 2004; 5: 77-187.
63. Wolf DH, Hilt W. The proteasome: a proteolytic nanomachine of cell regulation and waste disposal. Biochim Biophys Acta 2004; 1695: 19-31.
64. Madura K. Rad23 and Rpn10: perennial wallflowers join the mêlée. Trends Biochim Sci 2004; 29: 637-640.
65. Verma R, Oania R, Graumann J et al. Multiubiquitin chain receptors define a layer of substrate selectivity in the ubiquitin-proteasome system. Cell 2004; 118: 99-110.
66. Elsasser S, Finley D. Delivery of ubiquitinated substrates to protein/unfolding machines. Natur Cell Biol 2005; 7: 742-749.
67. Varadan R, Assfalg M, Raasi S et al. Structural determinants for selective recognition of a Lys48-linked polyubiquitin chain by a UBA domain. Mol Cell 2005; 18: 687-698.
68. Orlowski M, Wilk S. Ubiquitin-independent proteolytic functions of the proteasome. Arch Biochem Biphys 2003; 415: 1-5.
69. Hoyt MA, Coffino P. Ubiquitin-free routes into the proteasome. Cell Mol Life Sci 2004; 61: 1596-1600.
70. Chen X, Chi Y, Bloecher A et al. N-acetylation and ubiquitin-independent proteasomal degradation of p21 (Cip1). Mol Cell 2004; 16: 839-847.
71. Asher G, Bercovich Z, Tsvetkov P et al. 20S proteasomal degradation of ornithine decarboxylase is regulated by NQO1. Mol Cell 2005; 17: 645-655.
72. Asher G, Tsvetkov P, Kahana C et al. A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73. Genes Dev 2005; 19: 316-321.
73. Bellows DS, Tyers M. Chemical genetics hits “reality”. Science 2004; 306: 67-68.
74. Verma R., Peters NR, D‘ Onofrio M et al. Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain. Science 2004; 306: 117-120.
75. Špička I, Klener P. Inhibitory proteazomu - nová možnost léčby nádorových onemocnění. Čas Lék Čes 2004; 143: 701-704.
76. Burger AM, Seth AK. The ubiquitin-mediated protein degradation pathway in cancer: therapeutic implications. Europ J Cancer 2004; 40: 2217-2229.
77. Rajkumar V, Richardson PG, Hideshima T et al. Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol 2005; 23: 630-639.
78. Heemels M-T, Ploegh H. Generation, translocation, and presentation of MHC class I-restricted peptides. Annu Rev Biochem 1995; 64: 463-491.
79. Vigneron N, Stroobant V, Chapiro J et al. An antigenic peptide produced by peptide splicing in the proteasome. Science 2004; 304: 587-590.
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