Gliotoxin is a potent NOTCH2 transactivation inhibitor and efficiently induces apoptosis in chronic lymphocytic leukaemia (CLL) cells

British Journal of Haematology

Volumn 160, Issue 5, 2013, Pages 618-629

  Hubmann, Rainer ^a   Hilgarth, Martin ^a   Schnabl, Susanne ^a   Ponath, Elena ^a   Reiter, Marlies ^a   Demirtas, Dita ^a   Sieghart, Wolfgang ^a   Valent, Peter ^a,b   Zielinski, Christoph ^a   Jäger, Ulrich ^a   Shehata, Medhat ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b LUDWIG BOLTZMANN INSTITUTE FOR LUNG VASCULAR RESEARCH   (Austria)

Author keywords

Chronic lymphocytic leukaemia; Gliotoxin; NOTCH2; NR4A1

Indexed keywords

CD23 ANTIGEN; GLIOTOXIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NOTCH2 RECEPTOR; NOTCH3 RECEPTOR; NUCLEAR RECEPTOR NUR77;

ADULT; AGED; APOPTOSIS; ARTICLE; BONE MARROW CELL; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL ARTICLE; DOWN REGULATION; DRUG POTENCY; EX VIVO STUDY; FCER2 GENE; FEMALE; GEL MOBILITY SHIFT ASSAY; GENE; GENE EXPRESSION; HUMAN; HUMAN CELL; LEUKEMIA CELL; MALE; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STROMA CELL; TRANSCRIPTION REGULATION; TUMOR MICROENVIRONMENT;

AGED; AGED, 80 AND OVER; APOPTOSIS; CELL LINE, TUMOR; COCULTURE TECHNIQUES; DEPRESSION, CHEMICAL; DNA MUTATIONAL ANALYSIS; FEMALE; GENE EXPRESSION REGULATION, LEUKEMIC; GLIOTOXIN; HUMANS; IMMUNOGLOBULIN HEAVY CHAINS; INHIBITORY CONCENTRATION 50; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MIDDLE AGED; NEOPLASM PROTEINS; NF-KAPPA B; NUCLEAR RECEPTOR SUBFAMILY 4, GROUP A, MEMBER 1; PROTEASOME ENDOPEPTIDASE COMPLEX; RECEPTOR, NOTCH2; RECEPTORS, NOTCH; STROMAL CELLS; TRANSCRIPTION FACTORS; TRANSCRIPTIONAL ACTIVATION; TUMOR CELLS, CULTURED;

EID: 84873998594     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.12183     Document Type: Article

References (44)

1. Artavanis-Tsakonas, S., Rand, M.D. & Lake, R.J. (1999) Notch signaling: cell fate control and signal integration in development. Science, 284, 770-776.
2. Barragan, M., Bellosillo, B., Campas, C., Colomer, D., Pons, G. & Gil, J. (2002) Involvement of protein kinase C and phosphatidylinositol 3-kinase pathways in the survival of B-cell chronic lymphocytic leukemia cells. Blood, 99, 2969-2976.
3. Bikah, G., Carey, J., Ciallella, J.R., Tarakhovsky, A. & Bondada, S. (1996) CD5-mediated negative regulation of antigen receptor-induced growth signals in B-1 B cells. Science, 274, 1906-1909.
4. Borland, G., Edkins, A.L., Acharya, M., Matheson, J., White, L.J., Allen, J.M., Bonnefoy, J.Y., Ozanne, B.W. & Cushley, W. (2007) alphavbeta5 integrin sustains growth of human pre-B cells through an RGD-independent interaction with a basic domain of the CD23 protein. The Journal of Biological Chemistry, 282, 27315-27326.
5. Capobianco, A.J., Zagouras, P., Blaumueller, C.M., Artavanis-Tsakonas, S. & Bishop, J.M. (1997) Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2. Molecular and Cellular Biology, 17, 6265-6273.
6. Chiorazzi, N. & Ferrarini, M. (2003) B cell chronic lymphocytic leukemia: lessons learned from studies of the B cell antigen receptor. Annual Review of Immunology, 21, 841-894.
7. Coant, N., Ben Mkaddem, S., Pedruzzi, E., Guichard, C., Tréton, X., Ducroc, R., Freund, J.N., Cazals-Hatem, D., Bouhnik, Y., Woerther, P.L., Skurnik, D., Grodet, A., Fay, M., Biard, D., Lesuffleur, T., Deffert, C., Moreau, R., Groyer, A., Krause, K.H., Daniel, F. & Ogier-Denis, E. (2010) NADPH oxidase 1 modulates WNT and NOTCH1 signaling to control the fate of proliferative progenitor cells in the colon. Molecular and Cellular Biology, 30, 2636-2650.
8. Damle, R.N., Ghiotto, F., Valetto, A., Albesiano, E., Fais, F., Yan, X.J., Sison, C.P., Allen, S.L., Kolitz, J., Schulman, P., Vinciguerra, V.P., Budde, P., Frey, J., Rai, K.R., Ferrarini, M. & Chiorazzi, N. (2002) B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. Blood, 99, 4087-4093.
9. Das, I., Craig, C., Funahashi, Y., Jung, K.M., Kim, T.W., Byers, R., Weng, A.P., Kutok, J.L., Aster, J.C. & Kitajewski, J. (2004) Notch oncoproteins depend on gamma-secretase/presenilin activity for processing and function. The Journal of Biological Chemistry, 279, 30771-30780.
10. Duechler, M., Shehata, M., Schwarzmeier, J.D., Hoelbl, A., Hilgarth, M. & Hubmann, R. (2005) Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2. Leukemia, 19, 260-267.
11. Enders, A., Bouillet, P., Puthalakath, H., Xu, Y., Tarlinton, D.M. & Strasser, A. (2003) Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells. The Journal of Experimental Medicine, 198, 1119-1126.
12. Fabbri, G., Rasi, S., Rossi, D., Trifonov, V., Khiabanian, H., Ma, J., Grunn, A., Fangazio, M., Capello, D., Monti, S., Cresta, S., Gargiulo, E., Forconi, F., Guarini, A., Arcaini, L., Paulli, M., Laurenti, L., Larocca, L.M., Marasca, R., Gattei, V., Oscier, D., Bertoni, F., Mullighan, C.G., Foá, R., Pasqualucci, L., Rabadan, R., Dalla-Favera, R. & Gaidano, G. (2011) Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. The Journal of Experimental Medicine, 208, 1389-1401.
13. Gardiner, D.M., Waring, P. & Howlett, B.J. (2005) The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis. Microbiology, 151, 1021-1032.
14. Hubmann, R., Schwarzmeier, J.D., Shehata, M., Hilgarth, M., Duechler, M., Dettke, M. & Berger, R. (2002) Notch2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic leukemia. Blood, 99, 3742-3747.
15. Hubmann, R., Duchler, M., Schnabl, S., Hilgarth, M., Demirtas, D., Mitteregger, D., Hölbl, A., Vanura, K., Le, T., Look, T., Schwarzmeier, J.D., Valent, P., Jäger, U. & Shehata, M. (2010) NOTCH2 links protein kinase C delta to the expression of CD23 in chronic lymphocytic leukaemia (CLL) cells. British Journal of Haematology, 148, 868-878.
16. Hurne, A.M., Chai, C.L. & Waring, P. (2000) Inactivation of rabbit muscle creatine kinase by reversible formation of an internal disulfide bond induced by the fungal toxin gliotoxin. The Journal of Biological Chemistry, 275, 25202-25206.
17. Kovall, R.A. (2008) More complicated than it looks: assembly of Notch pathway transcription complexes. Oncogene, 27, 5099-5109.
18. Kroll, M., Arenzana-Seisdedos, F., Bachelerie, F., Thomas, D., Friguet, B. & Conconi, M. (1999) The secondary fungal metabolite gliotoxin targets proteolytic activities of the proteasome. Chemistry and Biology, 10, 689-698.
19. Lauring, A.S. & Overbaugh, J. (2000) Evidence that an IRES within the Notch2 coding region can direct expression of a nuclear form of the protein. Molecular Cell, 6, 939-945.
20. Lee, J.M., Lee, K.H., Weidner, M., Osborne, B.A. & Hayward, S.D. (2002) Epstein-Barr virus EBNA2 blocks Nur77- mediated apoptosis. Proceedings of the National Academy of Sciences of the United States of America, 99, 11878-11883.
21. Leong, K.G. & Karsan, A. (2006) Recent insights into the role of Notch signaling in tumorigenesis. Blood, 107, 2223-2233.
22. Lewis, R.E., Wiederhold, N.P., Chi, J., Han, X.Y., Komanduri, K.V., Kontoyiannis, D.P. & Prince, R.A. (2005) Detection of gliotoxin in experimental and human aspergillosis. Infection and Immunity, 73, 635-637.
23. Li, H., Kolluri, S.K., Gu, J., Dawson, M.I., Cao, X., Hobbs, P.D., Lin, B., Chen, G., Lu, J., Lin, F., Xie, Z., Fontana, J.A., Reed, J.C. & Zhang, X. (2000) Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science, 289, 1159-1164.
24. Lin, L., Mernaugh, R., Yi, F., Blum, D., Carbone, D.P. & Dang, T.P. (2010) Targeting specific regions of the Notch3 ligand-binding domain induces apoptosis and inhibits tumor growth in lung cancer. Cancer Research, 70, 632-638.
25. Mapara, M.Y., Weinmann, P., Bommert, K., Daniel, P.T., Bargou, R. & Dörken, B. (1995) Involvement of NAK-1, the human nur77 homologue, in surface IgM-mediated apoptosis in Burkitt lymphoma cell line BL41. European Journal of Immunology, 25, 2506-2510.
26. Miele, L. (2006) Notch signaling. Clinical Cancer Research, 12, 1074-1079.
27. Moll, U.M., Marchenko, N. & Zhang, X.K. (2006) p53 and Nur77/TR3 - transcription factors that directly target mitochondria for cell death induction. Oncogene, 25, 4725-4743.
28. Osipo, C., Golde, T.E., Osborne, B.A. & Miele, L.A. (2008) Off the beaten pathway: the complex cross talk between Notch and NF-kappaB. Laboratory Investigation, 88, 11-17.
29. Oswald, F., Liptay, S., Adler, G. & Schmid, R.M. (1998) NF-kappaB2 is a putative target gene of activated Notch-1 via RBP-Jkappa. Molecular and Cellular Biology, 18, 2077-2088.
30. Pahl, H.L., Krauss, B., Schulze-Osthoff, K., Decker, T., Traenckner, E.B., Vogt, M., Myers, C., Parks, T., Warring, P., Mühlbacher, A., Czernilofsky, A.P. & Baeuerle, P.A. (1996) The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB. The Journal of Experimental Medicine, 183, 1829-1840.
31. Puente, X.S., Pinyol, M., Quesada, V., Conde, L., Ordóñez, G.R., Villamor, N., Escaramis, G., Jares, P., Beà, S., González-Díaz, M., Bassaganyas, L., Baumann, T., Juan, M., López-Guerra, M., Colomer, D., Tubío, J.M., López, C., Navarro, A., Tornador, C., Aymerich, M., Rozman, M., Hernández, J.M., Puente, D.A., Freije, J.M., Velasco, G., Gutiérrez-Fernández, A., Costa, D., Carrió, A., Guijarro, S., Enjuanes, A., Hernández, L., Yagüe, J., Nicolás, P., Romeo-Casabona, C.M., Himmelbauer, H., Castillo, E., Dohm, J.C., de Sanjosé, S., Piris, M.A., de Alava, E., San Miguel, J., Royo, R., Gelpí, J.L., Torrents, D., Orozco, M., Pisano, D.G., Valencia, A., Guigó, R., Bayés, M., Heath, S., Gut, M., Klatt, P., Marshall, J., Raine, K., Stebbings, L.A., Futreal, P.A., Stratton, M.R., Campbell, P.J., Gut, I., López-Guillermo, A., Estivill, X., Montserrat, E., López-Otín, C. & Campo, E. (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature, 475, 101-105.
32. Rajpal, A., Cho, Y.A., Yelent, B., Koza-Taylor, P.H., Li, D., Chen, E., Whang, M., Kang, C., Turi, T.G. & Winoto, A. (2003) Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor. The EMBO Journal, 22, 6526-6536.
33. Ringshausen, I., Schneller, F., Bogner, C., Hipp, S., Duyster, J., Peschel, C. & Decker, T. (2002) Constitutively activated phosphatidylinositol-3 kinase (PI-3K) is involved in the defect of apoptosis in B-CLL: association with protein kinase Cdelta. Blood, 100, 3741-3748.
34. Rosati, E., Sabatini, R., Rampino, G., Tabilio, A., Di Ianni, M., Fettucciari, K., Bartoli, A., Coaccioli, S., Screpanti, I. & Marconi, P. (2009) Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells. Blood, 113, 856-865.
35. Saito, T., Chiba, S., Ichikawa, M., Kunisato, A., Asai, T., Shimizu, K., Yamaguchi, T., Yamamoto, G., Seo, S., Kumano, K., Nakagami-Yamaguchi, E., Hamada, Y., Aizawa, S. & Hirai, H. (2003) Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development. Immunity, 18, 675-685.
36. Secchiero, P., Melloni, E., di Iasio, M.G., Tiribelli, M., Rimondi, E., Corallini, F., Gattei, V. & Zauli, G. (2009) Nutlin-3 up-regulates the expression of Notch1 in both myeloid and lymphoid leukemic cells, as part of a negative feedback antiapoptotic mechanism. Blood, 113, 4300-4308.
37. Shehata, M., Schnabl, S., Demirtas, D., Hilgarth, M., Hubmann, R., Ponath, E., Badrnya, S., Lehner, C., Hoelbl, A., Duechler, M., Gaiger, A., Zielinski, C., Schwarzmeier, J.D. & Jaeger, U. (2010) Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3-K/Akt cascade counteract the antiapoptotic effect of human stromal cells in chronic lymphocytic leukemia. Blood, 116, 2513-2521.
38. Stanzani, M., Orciuolo, E., Lewis, R., Kontoyiannis, D.P., Martins, S.L., St John, L.S. & Komanduri, K.V. (2005) Aspergillus fumigatus suppresses the human cellular immune response via gliotoxin-mediated apoptosis of monocytes. Blood, 105, 2258-2265.
39. Sutton, P., Newcombe, N.R., Waring, P. & Mullbacher, A. (1994) In vivo immunosuppressive activity of gliotoxin, a metabolite produced by human pathogenic fungi. Infection and Immunity, 62, 1192-1198.
40. Tobe, M., Isobe, Y., Tomizawa, H., Nagasaki, T., Takahashi, H., Fukazawa, T. & Hayashi, H. (2003) Discovery of quinazolines as a novel structural class of potent inhibitors of NF-kappa B activation. Bioorganic & Medicinal Chemistry, 11, 383-391.
41. Tumang, J.R., Hastings, W.D., Bai, C. & Rothstein, T.L. (2004) Peritoneal and splenic B-1 cells are separable by phenotypic, functional, and transcriptomic characteristics. European Journal of Immunology, 34, 2158-2167.
42. Wang, Z., Li, Y., Banerjee, S. & Sarkar, F.H. (2008) Exploitation of the Notch signaling pathway as a novel target for cancer therapy. Anticancer Research, 28, 3621-3630.
43. Witt, C.M., Hurez, V., Swindle, C.S., Hamada, Y. & Klug, C.A. (2003) Activated Notch2 potentiates CD8 lineage maturation and promotes the selective development of B1 B cells. Molecular and Cellular Biology, 23, 8637-8650.
44. Zhu, J.H., Chen, C.L., Flavahan, S., Harr, J., Su, B. & Flavahan, N.A. (2011) Cyclic stretch stimulates vascular smooth muscle cell alignment by redox-dependent activation of Notch3. American Journal of Physiology. Heart and Circulatory Physiology, 300, 1770-1780.