The ubiquitin-proteasome system: A novel target for anticancer and anti-inflammatory drug research

• Autorzy: Ostrowska H
• Języki publikacji: EN

Abstrakty

EN

The ubiquitin-proteasome system is responsible for the degradation of most intracellular proteins, including those that control cell cycle progression, apoptosis, signal transduction and the NF-κB transcriptional pathway. Aberrations in the ubiquitin-proteasome system underlie the pathogenesis of many human diseases, so both the ubiquitin-conjugating system and the 20S proteasome are important targets for drug discovery. This article presents a few of the most important examples of the small molecule inhibitors and modulators targeting the ubiquitin-proteasome system, their mode of action, and their potential therapeutic relevance in the treatment of cancer and inflammatory-related diseases.

Słowa kluczowe

EN

ubiquitin-proteasome system; anticancer drug; antiinflammatory drug; cell cycle progression; control; apoptosis; signal transduction; pathogenesis; human disease; cancer; treatment

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2008
• Tom: 13
• Numer: 3
• Opis fizyczny: p.353-365,fig.,ref.

Twórcy

autor

Ostrowska H

• Medical University of Bialystok, Bialystok, Poland

Bibliografia

• 1. Glickman, M.H. and Ciechanover, A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 82 (2001) 373-428.
• 2. Ciechanover, A. and Schwartz, A.L. The ubiquitin system: pathogenesis of human diseases and drug targeting. Biochim. Biophys. Acta 1695 (2004) 3-7.
• 3. Herrmann, J., Ciechanover, A., Lerman, L.O. and Lerman, A. The ubiquitinproteasome system in cardiovascular diseases- a hypothesis extended. Cardiovasc. Res. 61(2004) 11-21.
• 4. Wojcik, C. and Di Napoli. M. Ubiquitin-proteasome system and proteasome inhibition: new strategies in stroke therapy. Stroke 35 (2004) 1506-1518.
• 5. Nalepa, G., Rolfe, M. and Harper, J.W. Drug discovery in the ubiquitinproteasome system. Nature 5 (2006) 596-623.
• 6. Burger, A. and Seth, A.K. The ubiquitin-mediated protein degradation pathway in cancer: therapeutic implications. Eur. J. Cancer 40 (2004) 2217-2229.
• 7. Sun, Y. E3 ubiquitin ligases as cancer targets and biomarkers. Neoplasia 8 (2006) 645-654.
• 8. Kisselev, A.F. and Goldberg, A.L. Proteasome inhibitors: from research tools to drug candidates. Chem. Biol. 8 (2001) 739-758.
• 9. Delcros, J.G., Floch, M.B., Prigent, C. and Arlot-Bonnemains, Y. Proteasome inhibitors as therapeutic agents: current and future strategies. Curr. Med. Chem. 10 (2003) 479-503.
• 10. Joazeiro, C.A.P., Anderson, K.C. and Hunter, T. Proteasome inhibitor drugs on the rise. Cancer Res. 66 (2006) 7840-7842.
• 11. Voorhees, P.M. and Orlowski, R.Z. The proteasome and proteasome inhibitors in cancer therapy. Annu. Rev. Pharmacol. Toxicol. 46 (2006) 189-213.
• 12. Orlowski, Z. The ubiquitin proteasome pathway from bench to bedside. Hematology 1 (2005) 220-225.
• 13. Zhou, P. Targeted protein degradation. Curr. Opin. Chem. Biol. 9 (2005) 51-55.
• 14. Michael, D. and Oren, M. The p53-Mdm2 module and the ubiquitin system. Semin. Cancer Biol. 13 (2003) 49-58.
• 15. Vassilev, L.T., Vu, B.T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., Fotouhi, N. and Liu, E.A. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303 (2004) 844-848.
• 16. Issaeva, N., Bozko, P., Enge, M., Protopopowa, M., Verhoef, L.G., Masucci, M., Pramanik, A. and Selivanova G. Small molecule RITA binds to p53, blocks p53-HDM2 interaction and activates p53 function in tumors. Nature Med. 10 (2004) 1321-1328.
• 17. Maerken, T.V., Speleman, F., Vermuelen, J., Lambertz, I., Clercq, S., Smet, E., Yigit, N., Coppens, V., Philippe, J., Paepe, A., Marine, J. and Vandesompele, J. Small-molecule MDM2 antagonists as a new therapy concept for neuroblastoma. Cancer Res. 66 (2006) 9646-9655.
• 18. Gstaiger, M., Jordan, R., Lim, M., Catzavelos, C., Mestan, J., Slingerland, J. and Krek, W. Skp2 is oncogenic and overexpressed in human cancers. Proc. Natl. Acad. Sci. (USA) 24 (2001) 5043-5048.
• 19. Baldwin, A.S. The transcription factor NF-κB and human diseases. J. Clin. Invest. 107 (2001) 3-6.
• 20. Karin, M. Nuclear factor-κB in cancer development and progression. Nature 44 (2006) 431-436.
• 21. Yamamoto, Y. and Gaynor, R.B. Therapeutic poteνtial of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. J. Clin. Invest. 107 (2001) 135-142.
• 22. Yaron, A., Gonen, H., Alkalay, I., Hatzubai, A., Jung, S., Beyth, S., Mercurio, F., Manning, A.M., Ciechanover, A., Ben-Neriah, Y. Inhibition of NF-κB cellular function via specific targeting of the IκB-ubiquitin ligase. EMBO J. 16 (1997) 6486-6494.
• 23. Swinney, D.C., Xu, Y.Z., Scarafia, L.E., Lee, I., Mak, A.Y., Gan, Q.F., Ramesha, C.S., Mulkins, M.A., Dunn, J., So, O.Y., Biegel, T., Dinh, M., Volkel, P., Barnett, J., Dalrymple, S.A., Lee, S. and Huber, M. A small molecule ubiquitination inhibitor blocks NF-κB-dependent cytokine expression in cells and rats. J. Biol. Chem. 277 (2002) 2357-23581.
• 24. Adams, J. Proteasome inhibitors as new anticancer drugs. Curr. Opin. Oncol. 14 (2002) 628-634.
• 25. Elliott, P.J., Zollner, T.M. and Boehncke, W.H. Proteasome inhibition: a new anti-inflammatory strategy. J. Mol. Med. 81 (2003) 235-245.
• 26. Orlowski, M and Wilk, S. Catalytic activities of the 20S proteasome, a multicatalytic proteinase complex. Arch. Biochem. Biophys. 383 (2000) 1-16.
• 27. Groll, M. and Huber, R. Inhibitors of eukaryotic 20S proteasome core particle: a structural approach. Biochim. Biophys. Acta 1695 (2004) 33-44.
• 28. Kloetzel, P.M. and Ossendorp, F. Proteasome and peptidase function in MHC class I-mediated antigen presentation. Curr. Opin. Immunol. 16 (2004) 76-81.
• 29. Groll, M. and Huber, R. Inhibitors of eukaryotic 20S proteasome core particle: a structural approach. Biochim. Biophys. Acta 1695 (2004) 33-44.
• 30. Hideshima, T., Richardson, P., Chauhan, D., Palombella, V.J., Elliot, P.J., Adams, J. and Anderson, K.C. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer. Res. 61 (2001) 3071-3076.
• 31. 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.
• 32. Adams, J. and Kauffman, M. Development of the proteasome inhibitor Velcade (Bortezomib). Cancer Invest. 22 (2004) 304-11.
• 33. Hideshima, T., Mitsiades, C., Akiyama, M., Hayashi, T., Chauhan, D., Richardson, P., Schlossman, R., Podar, K., Munshi, N.C., Mitsiades, N. and Anderson, K.C. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 101 (2003) 1530-1534.
• 34. Mitsiades, N., Mitsiades, C.S., Richardson, P.G., Poulaki, V., Tai, Y.Y., Chauhan, D., Fanourakis, G., Gu, X., Bailey, C., Joseph, M., Libermann, T.A., Schlossman, R., Munshi, N.C., Hideshima, T. and Anderson, K.C. The proteasome inhibitor PS-341 potentates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood 101 (2003) 2377-2380.
• 35. Vink. J., Cloos, J. and Kaspers, G.J.L. Proteasome inhibition as novel treatment strategy in leukaemia. Brit. J. Haematol. 134 (2006) 253-262.
• 36. 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. In. Ed. Engl. 42 (2003) 355-357.
• 37. Kuhn, D.J., Chen, Q., Voorhees, P.M., Strader, J.S., Shenk, K.D., Sun, C.M., Demo, S.D., Bennet, M.K., Leewen, F.W., Chanan-Khan, A.A. and Orlowski, R.Z. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against pre-clinical models of multiple myeloma. Blood (2007) prepublished online.
• 38. Ho, A., Bargagna-Mohan, P., Wehenkel, M., Mohan, R. and Kim, K. LMP2- specific inhibitors: chemical genetic tools for proteasome biology. Chem. Biol. 14 (2007) 419-430.
• 39. Chauhan, D., Catley, L., Li, G., Podar, K., Hideshima, T., Velankar, M., Mitsiades, N., Yasui, H., Letai, A., Ovaa, H., Berkers, C., Nicholson, B., Chao, T., Neuteboom, S.T., Richardson, P., Palladino, M.A. and Anderson, C. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from bortezomib. Cancer Cell 8 (2005) 407-419.
• 40. Ruiz, S., Krupnik, Y., Keating, M., Chandra, J., Palladino, M. and McConkey, D. The proteasome inhibitor NPI-0052 is a more effective inducer of apoptosis than bortezomib in lymphocytes from patients with chronic lymphocytic leukemia. Mol. Cancer Ther. 7 (2006) 1836-1843.
• 41. Stapnes, C., Doskeland, A.P., Hatfield, K., Ersvaer, E., Ryningen, A. and Lorens, J.B. The proteasome inhibitors bortezomib and PR-171 have antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cells. Brit. J. Haematol. 136 (2007) 814-828.
• 42. Di Napoli, M. and Papa, F. MLN-519: Milenium/PAION. Curr. Opin. Invest. Drugs 4 (2003) 333-341.
• 43. Phillips, J.B., Williams, A.J., Adams, J., Elliott, P.J. and Tortella, F.C. Proteasome inhibitor PS519 reduced infarction and attenuates leukocyte infiltration in a rat model of focal cerebral ischemia. Stroke 31 (2000) 1686- 1693.
• 44. Zhang, L., Zhang, Z.G., Zhang, R.L., Lu, M., Adams, J., Elliott, P.J. and Chopp, M. Postischemic (6-hour) treatment with recombinant human tissue plasminogen activator and proteasome inhibitor PS-519 reduces infarction in a rat model of embolic focal cerebral ischemia. Stroke 32 (2001) 2926-2931.
• 45. Berti, R., Williams, A.J., Velarde, L.C., Moffett, J.R., Elliott, P.J., Adams, J., Yao, C., Dave, J.R. and Tortella, F.C. Effect of the proteasome inhibitor MLN519 on the expression of inflammatory molecules following middle cerebral artery occlusion and reperfusion in the rat. Neurotox. Res. 5 (2003) 505-514.
• 46. Williams, A.J., Dave, J.R., Elliot, P.J., Adams, J. and Tortella, F.C. Delayed treatment of ischemic/reperfusion brain injury: extended therapeutic window with the proteasome inhibitor MLN519. Stroke 35 (2004) 1186-1191.
• 47. Williams, A.J., Dave, J.R. and Tortella, F.C. Neuroprotection with the proteasome inhibitor MLN519 in focal ischemic brain injury: relation to nuclear factor kappa B (NF-kappaB), inflammatory gene expression, and leukocyte infiltration. Neurochem. Int. 49 (2006) 106-112.
• 48. Campbell, B., Adams, J., Shin, Y.K. and Lefer, A.M. Cardioprotective effects of a novel proteasome inhibitor following ischemia and reperfusion in the isolated perfused rat heart. J. Mol. Cell Cardiol. 31 (1999) 467-476.
• 49. Pye. J., Ardeshirpour, F., McCain, A., Bellinger, D.A., Merricks, E., Adams, J., Elliott, P.J., Pien, C., Fisher, T.H., Baldwin, A.S. and Nichols, T.C. Proteasome inhibition ablates activation of NF-κB in myocardial reperfusion and reduces reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 264 (2003) H919-H926.
• 50. Stansfield, W.E., Moss, N.C., Willis, M.S., Tang, R. and Selzman, C.H. Proteasome inhibition attenuates infarct size and preserves cardiac function in a murine model of myocardial ischemia-reperfusion injury. Ann. Thorac. Surg. 84 (2007) 120-125.
• 51. Shah, I.M., Lees, K.R. and Elliott, P.J. Early clinical experience with the novel proteasome inhibitor PS-519. Brit. J. Clin. Pharmacol. 54 (2002) 269-276.
• 52. Buchan, A.M., Li, H. and Blackburn, B. Neuroprotection achieved with a novel proteasome inhibitor which blocks NF-kappaB activation. Neuroreport 11 (2000) 427-430.
• 53. Takaoka, M., Ohkita, M. and Matsumura, Y. Pathophysiological role of proteasome-dependent proteolytic pathway in endothelin-1-related cardiovascular diseases. Curr. Vasc. Pharmacol. 1 (2003) 19-26.
• 54. Itoh. M., Takaoka, M., Shibata, A., Okhita, M. and Matsumura, Y. Preventive effect of lactacystin, a selective proteasome inhibitor, on ischemic acute renal failure in rats. J. Pharmacol. Exp. Ther. 298 (2001) 501-507.
• 55. Ostrowska, J.K., Wojtukiewicz, M.Z., Chabielska, E., Buczko, W. and Ostrowska, H. Proteasome inhibitor prevents experimental arterial thrombosis in renovascular hypertensive rats. Thromb. Haemost. 92 (2004) 171-177.
• 56. Morgan, E.N., Pohlman, T.H. and Vocelka, C. Nuclear factor kappa B mediates a procoagulant response in monocytes during extracorporeal circulation. J. Thorac. Cardiovasc. Surg. 125 (2003) 165-171.
• 57. Ostrowska-Roszczenko, J.K., Ostrowska, H., Wojtukiewicz, M.Z., Radziwon, P., Szczepanski, M. and Wołczynski, S. Proteasome inhibition prevents tissue factor expression in human endothelial cells exposed to diverse agonists via inhibition of NF-kappaB in cultured endothelial cells. 41st Meeting of the Polish Biochem.Soc., Bialystok, 2006, 200.
• 58. Ostrowska, H., Wojcik, C., Omura, S. and Worowski, K. Lactacystin, a specific inhibitor of the proteasome, inhibits human platelet lysosomal cathepsin A-like enzyme. Biochem. Biophys. Res. Commun. 234 (1997) 729-732.
• 59. Geier, E., Pfeifer, G., Wilm, M., Lucchiari-Hartz, M., Baumeister, W., Eichmann, K. and Niedermann. G. A giant protease with potential to substitute for some functions of the proteasome. Science 283 (1999) 978-981.
• 60. Sakamoto, K.M. Kim, K.B., Kumagai, A., Mercurio, F., Crews, C.M. and Deshaies, R.J. Protacs: chimeric molecules that target proteins to the Skp1- cullin-F box complex for ubiquitination and degradation. Proc. Natl. Acad. Sci. 98 (2001) 8554-8559.
• 61. Zhang, D., Baek, S.H., Ho, A. and Kim, K. Degradation of target protein in living cells by small-molecule proteolysis inducers. Bioorg. Med. Chem. Lett. 14 (2004) 645-648.
• 62. Sakamoto, K.M., Kim, K.B., Verma, R., Ransick, A., Stein, B., Crews, C.M. and Deshaies, R.J. Development of protacs to target cancer-promoting proteins for ubiquitination and degradation. Mol. Cell. Proteomics 2 (2003) 1350-1358.