Molecular mechanism of 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced AXL receptor tyrosine kinase degradation

Journal of Biological Chemistry

Volumn 288, Issue 24, 2013, Pages 17481-17494

  Krishnamoorthy, Gnana Prakasam ^a   Guida, Teresa ^a   Alfano, Luigi ^a   Avilla, Elvira ^a   Santoro, Massimo ^a,b   Carlomagno, Francesca ^a,b   Melillo, Rosa Marina ^a,b  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b CNR   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI-CANCER THERAPIES; INTRACELLULAR COMPARTMENTS; INTRACELLULAR DOMAIN; MOLECULAR MECHANISM; POLYUBIQUITINATION; PROTEASOMAL DEGRADATION; RECEPTOR TYROSINE KINASE; THYROID CARCINOMA;

AMINO ACIDS; BIOACTIVITY; CELL MEMBRANES; PROTEINS;

ENZYMES;

BIOTIN; BOSUTINIB; HEAT SHOCK PROTEIN 90; METHIONINE; PROTEASOME; RADICICOL; TANESPIMYCIN; TYROSINE KINASE RECEPTOR; TYROSINE KINASE RECEPTOR AXL; UBIQUITIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CELL SURVIVAL; CHROMATIN IMMUNOPRECIPITATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; ENZYME DEGRADATION; ENZYME INHIBITION; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; INTRACELLULAR SIGNALING; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN GLYCOSYLATION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; RECEPTOR DOWN REGULATION; UBIQUITINATION;

17-AAG/GELDANAMYCIN; AXL RECEPTOR TYROSINE KINASE; CHIP E3 LIGASE; E3 UBIQUITIN LIGASE; HSP90; HSP90 INHIBITION; PROTEASOME; RECEPTOR TYROSINE KINASE; UBIQUITINATION;

ANILINE COMPOUNDS; ANTINEOPLASTIC AGENTS; BENZOQUINONES; CATALYTIC DOMAIN; CELL MEMBRANE; GLYCOSYLATION; HELA CELLS; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LACTAMS, MACROCYCLIC; LEUPEPTINS; NITRILES; PROTEASOME INHIBITORS; PROTEIN BINDING; PROTEIN ISOFORMS; PROTEIN KINASE INHIBITORS; PROTEIN STABILITY; PROTEIN TRANSPORT; PROTEOLYSIS; PROTO-ONCOGENE PROTEINS; QUINOLINES; RECEPTOR PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION;

EID: 84879058041     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.439422     Document Type: Article

References (51)

1. O'Bryan, J. P., Frye, R. A., Cogswell, P. C., Neubauer, A., Kitch, B., Prokop, C., Espinosa, R., 3rd, Le Beau, M. M., Earp, H. S., and Liu, E. T. (1991) Axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase. Mol. Cell. Biol. 11, 5016-5031 (Pubitemid 21895263)
2. Stitt, T. N., Conn, G., Gore, M., Lai, C., Bruno, J., Radziejewski, C., Mattsson, K., Fisher, J., Gies, D. R., Jones, P. F., Masiakowski, P., Ryan, T. E., Tobkes, N. J., Chen, D. H., DiStefano, P. S., Long, G. L., Basilico, C., Goldfarb, M. P., Lemke, G., Glass, D. J., and Yancopoulos, G. D. (1995) The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell 80, 661-670
3. Holland, S. J., Pan, A., Franci, C., Hu, Y., Chang, B., Li, W., Duan, M., Torneros, A., Yu, J., Heckrodt, T. J., Zhang, J., Ding, P., Apatira, A., Chua, J., Brandt, R., Pine, P., Goff, D., Singh, R., Payan, D. G., and Hitoshi, Y. (2010) R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res. 70, 1544-1554
4. Zhang, Y. X., Knyazev, P. G., Cheburkin, Y. V., Sharma, K., Knyazev, Y. P., Orfi, L., Szabadkai, I., Daub, H., Kéri, G., and Ullrich, A. (2008) AXL is a potential target for therapeutic intervention in breast cancer progression. Cancer Res. 68, 1905-1915 (Pubitemid 351416577)
5. Rankin, E. B., Fuh, K. C., Taylor, T. E., Krieg, A. J., Musser, M., Yuan, J., Wei, K., Kuo, C. J., Longacre, T. A., and Giaccia, A. J. (2010) AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res. 70, 7570-7579
6. Avilla, E., Guarino, V., Visciano, C., Liotti, F., Svelto, M., Krishnamoorthy, G., Franco, R., and Melillo, R. M. (2011) Activation of TYRO3/AXL tyrosine kinase receptors in thyroid cancer. Cancer Res. 71, 1792-1804
7. Huang, F., Hurlburt, W., Greer, A., Reeves, K. A., Hillerman, S., Chang, H., Fargnoli, J., Graf Finckenstein, F., Gottardis, M. M., and Carboni, J. M. (2010) Differential mechanisms of acquired resistance to insulin-like growth factor-I receptor antibody therapy or to a small-molecule inhibitor, BMS-754807, in a human rhabdomyosarcoma model. Cancer Res. 70, 7221-7231
8. Liu, L., Greger, J., Shi, H., Liu, Y., Greshock, J., Annan, R., Halsey, W., Sathe, G. M., Martin, A. M., and Gilmer, T. M. (2009) Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res. 69, 6871-6878
9. Hong, C. C., Lay, J. D., Huang, J. S., Cheng, A. L., Tang, J. L., Lin, M. T., Lai, G. M., and Chuang, S. E. (2008) Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia. Cancer Lett. 268, 314-324
10. Dufies, M., Jacquel, A., Belhacene, N., Robert, G., Cluzeau, T., Luciano, F., Cassuto, J. P., Raynaud, S., and Auberger, P. (2011) Mechanisms of AXL overexpression and function in Imatinib-resistant chronic myeloid leukemia cells. Oncotarget 2, 874-885
11. Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A. D., Rho, J. K., Choi, Y. J., Choi, C. M., Kim, S. W., Jang, S. J., Park, Y. S., Kim, W. S., Lee, D. H., Lee, J. S., Miller, V. A., Arcila, M., Ladanyi, M., Moonsamy, P., Sawyers, C., Boggon, T. J., Ma, P. C., Costa, C., Taron, M., Rosell, R., Halmos, B., and Bivona, T. G. (2012) Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat. Genet. 44, 852-860
12. Amann, J., Kalyankrishna, S., Massion, P. P., Ohm, J. E., Girard, L., Shigematsu, H., Peyton, M., Juroske, D., Huang, Y., Stuart Salmon, J., Kim, Y. H., Pollack, J. R., Yanagisawa, K., Gazdar, A., Minna, J. D., Kurie, J. M., and Carbone, D. P. (2005) Aberrant epidermal growth factor receptor signaling and enhanced sensitivity to EGFR inhibitors in lung cancer. Cancer Res. 65, 226-235 (Pubitemid 40070814)
13. Hanahan, D., and Weinberg, R. A. (2000) The hallmarks of cancer. Cell 100, 57-70 (Pubitemid 30046295)
14. Ali, M. M., Roe, S. M., Vaughan, C. K., Meyer, P., Panaretou, B., Piper, P. W., Prodromou, C., and Pearl, L. H. (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440, 1013-1017
15. Panaretou, B., Prodromou, C., Roe, S. M., O'Brien, R., Ladbury, J. E., Piper, P. W., and Pearl, L. H. (1998) ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. EMBO J. 17, 4829-4836 (Pubitemid 28377183)
16. Obermann, W. M., Sondermann, H., Russo, A. A., Pavletich, N. P., and Hartl, F. U. (1998) In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis. J. Cell Biol. 143, 901-910 (Pubitemid 28547391)
17. Welch, W. J. (1991) The role of heat-shock proteins as molecular chaperones. Curr. Opin. Cell Biol. 3, 1033-1038
18. Kundrat, L., and Regan, L. (2010) Balance between folding and degradation for Hsp90-dependent client proteins: a key role for CHIP. Biochemistry 49, 7428-7438
19. Supko, J. G., Hickman, R. L., Grever, M. R., and Malspeis, L. (1995) Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother. Pharmacol. 36, 305-315
20. Sausville, E. A., Tomaszewski, J. E., and Ivy, P. (2003) Clinical development of 17-allylamino, 17-demethoxygeldanamycin. Curr. Cancer Drug Targets 3, 377-383 (Pubitemid 37128324)
21. Schulte, T. W., and Neckers, L. M. (1998) The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother. Pharmacol. 42, 273-279 (Pubitemid 28393843)
22. Modi, S., Stopeck, A., Linden, H., Solit, D., Chandarlapaty, S., Rosen, N., D'Andrea, G., Dickler, M., Moynahan, M. E., Sugarman, S., Ma, W., Patil, S., Norton, L., Hannah, A. L., and Hudis, C. (2011) HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin. Cancer Res. 17, 5132-5139
23. Neckers, L., and Workman, P. (2012) Hsp90 molecular chaperone inhibitors: are we there yet? Clin. Cancer Res. 18, 64-76
24. Santoro, M., Carlomagno, F., Romano, A., Bottaro, D. P., Dathan, N. A., Grieco, M., Fusco, A., Vecchio, G., Matoskova, B., Kraus, M. H., and Di Fiore, P. P. (1995) Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 267, 381-383
25. García-Cardeña, G., Fan, R., Shah, V., Sorrentino, R., Cirino, G., Papapetropoulos, A., and Sessa, W. C. (1998) Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 392, 821-824 (Pubitemid 28225323)
26. Guida, T., Anaganti, S., Provitera, L., Gedrich, R., Sullivan, E., Wilhelm, S. M., Santoro, M., and Carlomagno, F. (2007) Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor β gatekeeper mutants. Clin. Cancer Res. 13, 3363-3369 (Pubitemid 46944924)
27. Gottardi, C. J., Dunbar, L. A., and Caplan, M. J. (1995) Biotinylation and assessment of membrane polarity: caveats and methodological concerns. Am. J. Physiol. Renal Physiol. 268, F285-F295
28. Ghosh, A. K., Secreto, C., Boysen, J., Sassoon, T., Shanafelt, T. D., Mukhopadhyay, D., and Kay, N. E. (2011) The novel receptor tyrosine kinase Axl is constitutively active in B-cell chronic lymphocytic leukemia and acts as a docking site of nonreceptor kinases: implications for therapy. Blood 117, 1928-1937
29. Carlomagno, F., De Vita, G., Berlingieri, M. T., de Franciscis, V., Melillo, R. M., Colantuoni, V., Kraus, M. H., Di Fiore, P. P., Fusco, A., and Santoro, M. (1996) Molecular heterogeneity of RET loss of function in Hirschsprung's disease. EMBO J. 15, 2717-2725 (Pubitemid 26176249)
30. Neckers, L., Schulte, T. W., and Mimnaugh, E. (1999) Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Invest. New Drugs 17, 361-373 (Pubitemid 30135903)
31. Xu, W., Yuan, X., Xiang, Z., Mimnaugh, E., Marcu, M., and Neckers, L. (2005) Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex. Nat. Struct. Mol. Biol. 12, 120-126
32. Murata, S., Chiba, T., and Tanaka, K. (2003) CHIP: a quality-control E3 ligase collaborating with molecular chaperones. Int. J. Biochem. Cell Biol. 35, 572-578 (Pubitemid 36369506)
33. Meacham, G. C., Patterson, C., Zhang, W., Younger, J. M., and Cyr, D. M. (2001) The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat. Cell Biol. 3, 100-105 (Pubitemid 32114840)
34. Murata, S., Minami, Y., Minami, M., Chiba, T., and Tanaka, K. (2001) CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2, 1133-1138 (Pubitemid 34055961)
35. Xu, W., Marcu, M., Yuan, X., Mimnaugh, E., Patterson, C., and Neckers, L. (2002) Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu. Proc. Natl. Acad. Sci. U.S.A. 99, 12847-12852
36. Alfano, L., Guida, T., Provitera, L., Vecchio, G., Billaud, M., Santoro, M., and Carlomagno, F. (2010) RET is a heat shock protein 90 (HSP90) client protein and is knocked down upon HSP90 pharmacological block. J. Clin. Endocrinol. Metab. 95, 3552-3557
37. Zhou, P., Fernandes, N., Dodge, I. L., Reddi, A. L., Rao, N., Safran, H., DiPetrillo, T. A., Wazer, D. E., Band, V., and Band, H. (2003) ErbB2 degradation mediated by the co-chaperone protein CHIP. J. Biol. Chem. 278, 13829-13837 (Pubitemid 36799921)
38. Morishima, Y., Wang, A. M., Yu, Z., Pratt, W. B., Osawa, Y., and Lieberman, A. P. (2008) CHIP deletion reveals functional redundancy of E3 ligases in promoting degradation of both signaling proteins and expanded glutamine proteins. Hum. Mol. Genet. 17, 3942-3952 (Pubitemid 352762855)
39. Tikhomirov, O., and Carpenter, G. (2003) Identification of ErbB-2 kinase domain motifs required for geldanamycin-induced degradation. Cancer Res. 63, 39-43 (Pubitemid 36070417)
40. Xu, W., Mimnaugh, E., Rosser, M. F., Nicchitta, C., Marcu, M., Yarden, Y., and Neckers, L. (2001) Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90. J. Biol. Chem. 276, 3702-3708
41. Citri, A., Alroy, I., Lavi, S., Rubin, C., Xu, W., Grammatikakis, N., Patterson, C., Neckers, L., Fry, D. W., and Yarden, Y. (2002) Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy. EMBO J. 21, 2407-2417 (Pubitemid 34546713)
42. Fumo, G., Akin, C., Metcalfe, D. D., and Neckers, L. (2004) 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells. Blood 103, 1078-1084 (Pubitemid 38129574)
43. Matei, D., Satpathy, M., Cao, L., Lai, Y. C., Nakshatri, H., and Donner, D. B. (2007) The platelet-derived growth factor receptor α is destabilized by geldanamycins in cancer cells. J. Biol. Chem. 282, 445-453 (Pubitemid 47076653)
44. Farina, A. R., Tacconelli, A., Cappabianca, L., Cea, G., Chioda, A., Romanelli, A., Pensato, S., Pedone, C., Gulino, A., and Mackay, A. R. (2009) The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells. Oncogene 28, 4075-4094
45. Citri, A., Harari, D., Shohat, G., Ramakrishnan, P., Gan, J., Lavi, S., Eisenstein, M., Kimchi, A., Wallach, D., Pietrokovski, S., and Yarden Y. (2006) Hsp90 recognizes a common surface on client kinases. J. Biol. Chem. 281, 14361-14369 (Pubitemid 43848365)
46. Shimamura, T., Lowell, A. M., Engelman, J. A., and Shapiro, G. I. (2005) Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins. Cancer Res. 65, 6401-6408 (Pubitemid 40994428)
47. Taipale, M., Krykbaeva, I., Koeva, M., Kayatekin, C., Westover, K. D., Karras, G. I., and Lindquist, S. (2012) Quantitative analysis of Hsp90-client interactions reveals principles of substrate recognition. Cell 150, 987-1001
48. Li, Y., Ye, X., Tan, C., Hongo, J. A., Zha, J., Liu, J., Kallop, D., Ludlam, M. J., and Pei, L. (2009) Axl as a potential therapeutic target in cancer: role of Axl in tumor growth, metastasis and angiogenesis. Oncogene 28, 3442-3455
49. Ramalingam, S. S., Egorin, M. J., Ramanathan, R. K., Remick, S. C., Sikorski, R. P., Lagattuta, T. F., Chatta, G. S., Friedland, D. M., Stoller, R. G., Potter, D. M., Ivy, S. P., and Belani, C. P. (2008) A phase I study of 17-allylamino-17-demethoxygeldanamycin combined with paclitaxel in patients with advanced solid malignancies. Clin. Cancer Res. 14, 3456-3461
50. Hubbard, J., Erlichman, C., Toft, D. O., Qin, R., Stensgard, B. A., Felten, S., Ten Eyck, C., Batzel, G., Ivy, S. P., and Haluska, P. (2011) Phase I study of 17-allylamino-17 demethoxygeldanamycin, gemcitabine and/or cisplatin in patients with refractory solid tumors. Invest. New Drugs 29, 473- 480
51. Iyer, G., Morris, M. J., Rathkopf, D., Slovin, S. F., Steers, M., Larson, S. M., Schwartz, L. H., Curley, T., DeLaCruz, A., Ye, Q., Heller, G., Egorin, M. J., Ivy, S. P., Rosen, N., Scher, H. I., and Solit, D. B. (2012) A phase I trial of docetaxel and pulse-dose 17-allylamino-17-demethoxygeldanamycin in adult patients with solid tumors. Cancer Chemother. Pharmacol. 69, 1089-1097