Lipid raft-mediated Fas/CD95 apoptotic signaling in leukemic cells and normal leukocytes and therapeutic implications

Journal of Leukocyte Biology

Volumn 98, Issue 5, 2015, Pages 739-759

  Gajate, Consuelo ^a   Mollinedo, Faustino ^a  

^a UNIVERSITY OF SALAMANCA   (Spain)

Author keywords

Autoimmune disease; Cancer; Death receptor

Indexed keywords

ANTINEOPLASTIC AGENT; CASPASE 10; CASPASE 7; CASPASE 8; CD74 ANTIGEN; CERAMIDE; CLOFARABINE; DEATH RECEPTOR 4; DEATH RECEPTOR 5; EDELFOSINE; FAS ASSOCIATED DEATH DOMAIN PROTEIN; FAS LIGAND; GEMCITABINE; HEAT SHOCK PROTEIN 90; MILATUZUMAB; MIXED LINEAGE KINASE 3; PHOSPHATIDYLINOSITOL 3 KINASE; PROCASPASE 8; PROTEIN KINASE B; SPHINGOMYELIN; SPHINGOMYELIN PHOSPHODIESTERASE; STRESS ACTIVATED PROTEIN KINASE; FAS ANTIGEN; FAS PROTEIN, HUMAN;

ACUTE MYELOBLASTIC LEUKEMIA; APOPTOSIS; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; CANCER CHEMOTHERAPY; CANCER SURVIVAL; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL FATE; CELL MEMBRANE; CELL PROLIFERATION; CELL SURVIVAL; CYTOTOXIC T LYMPHOCYTE; ENDOPLASMIC RETICULUM; ENZYME PHOSPHORYLATION; EXOSOME; GENE EXPRESSION; GERMLINE MUTATION; HUMAN; IMMUNOLOGICAL TOLERANCE; INTERNALIZATION; JURKAT CELL LINE; LEUKEMIA CELL; LEUKOCYTE; LIPID RAFT; LYMPHATIC LEUKEMIA; LYMPHOCYTE ACTIVATION; MACROPHAGE; MULTIPLE SCLEROSIS; NEUTROPHIL; NONHUMAN; PALMITOYLATION; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; REVIEW; S PALMITOYLATION; SIGNAL TRANSDUCTION; T CELL LEUKEMIA; UPREGULATION; ANIMAL; IMMUNOLOGY; LEUKEMIA; PATHOLOGY; T LYMPHOCYTE;

ANIMALS; ANTIGENS, CD95; APOPTOSIS; CELL SURVIVAL; HUMANS; LEUKEMIA; MEMBRANE MICRODOMAINS; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 84946055153     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1189/jlb.2MR0215-055R     Document Type: Review

References (280)

1. Simons, K., Ikonen, E. (1997) Functional rafts in cell membranes. Nature 387, 569-572.
2. Simons, K., Toomre, D. (2000) Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 1, 31-39.
3. Ikonen, E. (2001) Roles of lipid rafts in membrane transport. Curr. Opin. Cell Biol. 13, 470-477.
4. Pike, L. J. (2006) Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell Function. J. Lipid Res. 47, 1597-1598.
5. Israelachvili, J. N., Marcelja, S., Horn, R. G. (1980) Physical principles of membrane organization. Q. Rev. Biophys. 13, 121-200.
6. Browning, J. L. (1981) Motions and interactions of phospholipid head groups at the membrane surface. 2. Simple alkyl head groups. Biochemistry 20, 7123-7133.
7. Jiang, Z., Redfern, R. E., Isler, Y., Ross, A. H., Gericke, A. (2014) Cholesterol stabilizes fluid phosphoinositide domains. Chem. Phys. Lipids 182, 52-61.
8. Owen, D. M., Gaus, K., Magee, A. I., Cebecauer, M. (2010) Dynamic organization of lymphocyte plasma membrane: lessons from advanced imaging methods. Immunology 131, 1-8.
9. Simons, K., Gerl, M. J. (2010) Revitalizing membrane rafts: new tools and insights. Nat. Rev. Mol. Cell Biol. 11, 688-699.
10. Simons, K., Sampaio, J. L. (2011) Membrane organization and lipid rafts. Cold Spring Harb. Perspect. Biol. 3, a004697.
11. Zhuang, L., Lin, J., Lu, M. L., Solomon, K. R., Freeman, M. R. (2002) Cholesterol-rich lipid rafts mediate akt-regulated survival in prostate cancer cells. Cancer Res. 62, 2227-2231.
12. Alicia, S., Angélica, Z., Carlos, S., Alfonso, S., Vaca, L. (2008) STIM1 converts TRPC1 from a receptor-operated to a store-operated channel: moving TRPC1 in and out of lipid rafts. Cell Calcium 44, 479-491.
13. Calay, D., Vind-Kezunovic, D., Frankart, A., Lambert, S., Poumay, Y., Gniadecki, R. (2010) Inhibition of Akt signaling by exclusion from lipid rafts in normal and transformed epidermal keratinocytes. J. Invest. Dermatol. 130, 1136-1145.
14. Mollinedo, F., Gajate, C. (2015) Lipid rafts as major platforms for signaling regulation in cancer. Adv. Biol. Regul. 57, 130-146.
15. Brown, D. A., London, E. (1997) Structure of detergent-resistant membrane domains: does phase separation occur in biological membranes? Biochem. Biophys. Res. Commun. 240, 1-7.
16. Schroeder, R. J., Ahmed, S. N., Zhu, Y., London, E., Brown, D. A. (1998) Cholesterol and sphingolipid enhance the Triton X-100 insolubility of glycosylphosphatidylinositol-anchored proteins by promoting the formation of detergent-insoluble ordered membrane domains. J. Biol. Chem. 273, 1150-1157.
17. Hell, S. W., Wichmann, J. (1994) Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. Opt. Lett. 19, 780-782.
18. Eggeling, C., Ringemann, C., Medda, R., Schwarzmann, G., Sandhoff, K., Polyakova, S., Belov, V. N., Hein, B., von Middendorff, C., Schönle, A., Hell, S. W. (2009) Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457, 1159-1162.
19. Sharma, P., Varma, R., Sarasij, R. C., Ira, Gousset, K., Krishnamoorthy, G., Rao, M., Mayor, S. (2004) Nanoscale organization of multiple GPI-anchored proteins in living cell membranes. Cell 116, 577-589.
20. Vyas, N., Goswami, D., Manonmani, A., Sharma, P., Ranganath, H. A., VijayRaghavan, K., Shashidhara, L. S., Sowdhamini, R., Mayor, S. (2008) Nanoscale organization of hedgehog is essential for long-range signaling. Cell 133, 1214-1227.
21. Gaus, K., Gratton, E., Kable, E. P., Jones, A. S., Gelissen, I., Kritharides, L., Jessup, W. (2003) Visualizing lipid structure and raft domains in living cells with two-photon microscopy. Proc. Natl. Acad. Sci. USA 100, 15554-15559.
22. Schneckenburger, H. (2005) Total internal reflection fluorescence microscopy: technical innovations and novel applications. Curr. Opin. Biotechnol. 16, 13-18.
23. Asanov, A., Zepeda, A., Vaca, L. (2010) A novel form of total internal reflection fluorescence microscopy (LG-TIRFM) reveals different and independent lipid raft domains in living cells. Biochim. Biophys. Acta 1801, 147-155.
24. Betzig, E., Patterson, G. H., Sougrat, R., Lindwasser, O. W., Olenych, S., Bonifacino, J. S., Davidson, M. W., Lippincott-Schwartz, J., Hess, H. F. (2006) Imaging intracellular fluorescent proteins at nanometer resolution. Science 313, 1642-1645.
25. Owen, D. M., Rentero, C., Rossy, J., Magenau, A., Williamson, D., Rodriguez, M., Gaus, K. (2010) PALM imaging and cluster analysis of protein heterogeneity at the cell surface. J. Biophotonics 3, 446-454.
26. Wang, J., Richards, D. A. (2012) Segregation of PIP2 and PIP3 into distinct nanoscale regions within the plasma membrane. Biol. Open 1, 857-862.
27. Mollinedo, F. (2012) Lipid raft involvement in yeast cell growth and death. Front. Oncol. 2, 140.
28. Heerklotz, H. (2002) Triton promotes domain formation in lipid raft mixtures. Biophys. J. 83, 2693-2701.
29. Munro, S. (2003) Lipid rafts: elusive or illusive? Cell 115, 377-388.
30. Lichtenberg, D., Goñi, F. M., Heerklotz, H. (2005) Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem. Sci. 30, 430-436.
31. Lingwood, D., Simons, K. (2007) Detergent resistance as a tool in membrane research. Nat. Protoc. 2, 2159-2165.
32. Maxfield, F. R. (2002) Plasma membrane microdomains. Curr. Opin. Cell Biol. 14, 483-487.
33. Gao, X., Lowry, P. R., Zhou, X., Depry, C., Wei, Z., Wong, G. W., Zhang, J. (2011) PI3K/Akt signaling requires spatial compartmentalization in plasma membrane microdomains. Proc. Natl. Acad. Sci. USA 108, 14509-14514.
34. Adam, R. M., Mukhopadhyay, N. K., Kim, J., Di Vizio, D., Cinar, B., Boucher, K., Solomon, K. R., Freeman, M. R. (2007) Cholesterol sensitivity of endogenous and myristoylated Akt. Cancer Res. 67, 6238-6246.
35. Mollinedo, F., Gajate, C. (2006) Fas/CD95 death receptor and lipid rafts: new targets for apoptosis-directed cancer therapy. Drug Resist. Updat. 9, 51-73.
36. Mollinedo, F., de la Iglesia-Vicente, J., Gajate, C., Estella-Hermoso de Mendoza, A., Villa-Pulgarin, J. A., Campanero, M. A., Blanco-Prieto, M. J. (2010) Lipid raft-targeted therapy in multiple myeloma. Oncogene 29, 3748-3757.
37. Gajate, C., Mollinedo, F. (2014) Lipid rafts, endoplasmic reticulum and mitochondria in the antitumor action of the alkylphospholipid analog edelfosine. Anticancer. Agents Med. Chem. 14, 509-527.
38. Mollinedo, F., Fernández-Luna, J. L., Gajate, C., Martín-Martín, B., Benito, A., Martínez-Dalmau, R., Modolell, M. (1997) Selective induction of apoptosis in cancer cells by the ether lipid ET-18-OCH3 (Edelfosine): molecular structure requirements, cellular uptake, and protection by Bcl-2 and Bcl-XL. Cancer Res. 57, 1320-1328.
39. Ruiter, G. A., Zerp, S. F., Bartelink, H., van Blitterswijk, W. J., Verheij, M. (1999) Alkyl-lysophospholipids activate the SAPK/JNK pathway and enhance radiation-induced apoptosis. Cancer Res. 59, 2457-2463.
40. Gajate, C., Fonteriz, R. I., Cabaner, C., Alvarez-Noves, G., Alvarez- Rodriguez, Y., Modolell, M., Mollinedo, F. (2000) Intracellular triggering of Fas, independently of FasL, as a new mechanism of antitumor ether lipid-induced apoptosis. Int. J. Cancer 85, 674-682.
41. Gajate, C., Mollinedo, F. (2002) Biological activities, mechanisms of action and biomedical prospect of the antitumor ether phospholipid ET-18-OCH3 (edelfosine), a proapoptotic agent in tumor cells. Curr. Drug Metab. 3, 491-525.
42. Gajate, C., Del Canto-Jañez, E., Acuña, A. U., Amat-Guerri, F., Geijo, E., Santos-Beneit, A. M., Veldman, R. J., Mollinedo, F. (2004) Intracellular triggering of Fas aggregation and recruitment of apoptotic molecules into Fas-enriched rafts in selective tumor cell apoptosis. J. Exp. Med. 200, 353-365.
43. Mollinedo, F. (2007) Antitumor ether lipids: proapoptotic agents with multiple therapeutic indications. Expert Opin. Ther. Pat. 17, 385-405.
44. Mollinedo, F. (2014) Editorial: Antitumor alkylphospholipid analogs: a promising and growing family of synthetic cell membrane-targeting molecules for cancer treatment). Anticancer. Agents Med. Chem. 14, 495-498.
45. Mollinedo, F., Gajate, C., Martín-Santamaría, S., Gago, F. (2004) ET-18- OCH3 (edelfosine): a selective antitumour lipid targeting apoptosis through intracellular activation of Fas/CD95 death receptor. Curr. Med. Chem. 11, 3163-3184.
46. Wajant, H. (2014) Principles and mechanisms of CD95 activation. Biol. Chem. 395, 1401-1416.
47. Fouqué, A., Debure, L., Legembre, P. (2014) The CD95/CD95L signaling pathway: a role in carcinogenesis. Biochim. Biophys. Acta 1846, 130-141.
48. Tibbetts, M. D., Zheng, L., Lenardo, M. J. (2003) The death effector domain protein family: regulators of cellular homeostasis. Nat. Immunol. 4, 404-409.
49. Kischkel, F. C., Hellbardt, S., Behrmann, I., Germer, M., Pawlita, M., Krammer, P. H., Peter, M. E. (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 14, 5579-5588.
50. Muzio, M., Stockwell, B. R., Stennicke, H. R., Salvesen, G. S., Dixit, V. M. (1998) An induced proximity model for caspase-8 activation. J. Biol. Chem. 273, 2926-2930.
51. Dickens, L. S., Boyd, R. S., Jukes-Jones, R., Hughes, M. A., Robinson, G. L., Fairall, L., Schwabe, J. W., Cain, K., Macfarlane, M. (2012) A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol. Cell 47, 291-305.
52. Schleich, K., Warnken, U., Fricker, N., Ozt ürk, S., Richter, P., Kammerer, K., Schnölzer, M., Krammer, P. H., Lavrik, I. N. (2012) Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model. Mol. Cell 47, 306-319.
53. Barnhart, B. C., Alappat, E. C., Peter, M. E. (2003) The CD95 type I/type II model. Semin. Immunol. 15, 185-193.
54. Vogler, M., Walczak, H., Stadel, D., Haas, T. L., Genze, F., Jovanovic, M., Gschwend, J. E., Simmet, T., Debatin, K. M., Fulda, S. (2008) Targeting XIAP bypasses Bcl-2-mediated resistance to TRAIL and cooperates with TRAIL to suppress pancreatic cancer growth in vitro and in vivo. Cancer Res. 68, 7956-7965.
55. Jost, P. J., Grabow, S., Gray, D., McKenzie, M. D., Nachbur, U., Huang, D. C., Bouillet, P., Thomas, H. E., Borner, C., Silke, J., Strasser, A., Kaufmann, T. (2009) XIAP discriminates between type I and type II FAS-induced apoptosis. Nature 460, 1035-1039.
56. Barnhart, B. C., Legembre, P., Pietras, E., Bubici, C., Franzoso, G., Peter, M. E. (2004) CD95 ligand induces motility and invasiveness of apoptosisresistant tumor cells. EMBO J. 23, 3175-3185.
57. Reichmann, E. (2002) The biological role of the Fas/FasL system during tumor formation and progression. Semin. Cancer Biol. 12, 309-315.
58. Shinohara, H., Yagita, H., Ikawa, Y., Oyaizu, N. (2000) Fas drives cell cycle progression in glioma cells via extracellular signal-regulated kinase activation. Cancer Res. 60, 1766-1772.
59. Steller, E. J., Borel Rinkes, I. H., Kranenburg, O. (2011) How CD95 stimulates invasion. Cell Cycle 10, 3857-3862.
60. Steller, E. J., Ritsma, L., Raats, D. A., Hoogwater, F. J., Emmink, B. L., Govaert, K. M., Laoukili, J., Rinkes, I. H., van Rheenen, J., Kranenburg, O. (2011) The death receptor CD95 activates the cofilin pathway to stimulate tumour cell invasion. EMBO Rep. 12, 931-937.
61. Ehrenschwender, M., Siegmund, D., Wicovsky, A., Kracht, M., Dittrich- Breiholz, O., Spindler, V., Waschke, J., Kalthoff, H., Trauzold, A., Wajant, H. (2010) Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation. Cell Death Differ. 17, 1435-1447.
62. Worth, A., Thrasher, A. J., Gaspar, H. B. (2006) Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical phenotype. Br. J. Haematol. 133, 124-140.
63. Shah, S., Wu, E., Rao, V. K., Tarrant, T. K. (2014) Autoimmune lymphoproliferative syndrome: an update and review of the literature. Curr. Allergy Asthma Rep. 14, 462.
64. Bleesing, J. J., Straus, S. E., Fleisher, T. A. (2000) Autoimmune lymphoproliferative syndrome. A human disorder of abnormal lymphocyte survival. Pediatr. Clin. North Am. 47, 1291-1310.
65. Straus, S. E., Jaffe, E. S., Puck, J. M., Dale, J. K., Elkon, K. B., Rösen- Wolff, A., Peters, A. M., Sneller, M. C., Hallahan, C. W., Wang, J., Fischer, R. E., Jackson, C. M., Lin, A. Y., Bäumler, C., Siegert, E., Marx, A., Vaishnaw, A. K., Grodzicky, T., Fleisher, T. A., Lenardo, M. J. (2001) The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis. Blood 98, 194-200.
66. Teachey, D. T. (2012) New advances in the diagnosis and treatment of autoimmune lymphoproliferative syndrome. Curr. Opin. Pediatr. 24, 1-8.
67. Oliveira, J. B., Bleesing, J. J., Dianzani, U., Fleisher, T. A., Jaffe, E. S., Lenardo, M. J., Rieux-Laucat, F., Siegel, R. M., Su, H. C., Teachey, D. T., Rao, V. K. (2010) Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood 116, e35-e40.
68. Dowdell, K. C., Niemela, J. E., Price, S., Davis, J., Hornung, R. L., Oliveira, J. B., Puck, J. M., Jaffe, E. S., Pittaluga, S., Cohen, J. I., Fleisher, T. A., Rao, V. K. (2010) Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome. Blood 115, 5164-5169.
69. Wu, J., Wilson, J., He, J., Xiang, L., Schur, P. H., Mountz, J. D. (1996) Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease. J. Clin. Invest. 98, 1107-1113.
70. Price, S., Shaw, P. A., Seitz, A., Joshi, G., Davis, J., Niemela, J. E., Perkins, K., Hornung, R. L., Folio, L., Rosenberg, P. S., Puck, J. M., Hsu, A. P., Lo, B., Pittaluga, S., Jaffe, E. S., Fleisher, T. A., Rao, V. K., Lenardo, M. J. (2014) Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood 123, 1989-1999.
71. Cohen, P. L., Eisenberg, R. A. (1991) Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu. Rev. Immunol. 9, 243-269.
72. Sneller, M. C., Straus, S. E., Jaffe, E. S., Jaffe, J. S., Fleisher, T. A., Stetler- Stevenson, M., Strober, W. (1992) A novel lymphoproliferative/ autoimmune syndrome resembling murine lpr/gld disease. J. Clin. Invest. 90, 334-341.
73. Takahashi, T., Tanaka, M., Brannan, C. I., Jenkins, N. A., Copeland, N. G., Suda, T., Nagata, S. (1994) Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76, 969-976.
74. Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A., Nagata, S. (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356, 314-317.
75. Chu, J. L., Drappa, J., Parnassa, A., Elkon, K. B. (1993) The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn. J. Exp. Med. 178, 723-730.
76. Matsuzawa, A., Moriyama, T., Kaneko, T., Tanaka, M., Kimura, M., Ikeda, H., Katagiri, T. (1990) A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse. J. Exp. Med. 171, 519-531.
77. Imtiyaz, H. Z., Zhang, Y., Zhang, J. (2005) Structural requirements for signal-induced target binding of FADD determined by functional reconstitution of FADD deficiency. J. Biol. Chem. 280, 31360-31367.
78. Nose, M., Nishihara, M., Kamogawa, J., Terada, M., Nakatsuru, S. (2000) Genetic basis of autoimmune disease in MRL/lpr mice: dissection of the complex pathological manifestations and their susceptibility loci. Rev. Immunogenet. 2, 154-164.
79. Lowin, B., Hahne, M., Mattmann, C., Tschopp, J. (1994) Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 370, 650-652.
80. Streilein, J. W. (2003) Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J. Leukoc. Biol. 74, 179-185.
81. Griffith, T. S., Brunner, T., Fletcher, S. M., Green, D. R., Ferguson, T. A. (1995) Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 270, 1189-1192.
82. Via, C. S., Nguyen, P., Shustov, A., Drappa, J., Elkon, K. B. (1996) A major role for the Fas pathway in acute graft-versus-host disease. J. Immunol. 157, 5387-5393.
83. O'Connell, J., Bennett, M. W., O'Sullivan, G. C., Collins, J. K., Shanahan, F. (1999) The Fas counterattack: cancer as a site of immune privilege. Immunol. Today 20, 46-52.
84. Iwai, K., Miyawaki, T., Takizawa, T., Konno, A., Ohta, K., Yachie, A., Seki, H., Taniguchi, N. (1994) Differential expression of bcl-2 and susceptibility to anti-Fas-mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils. Blood 84, 1201-1208.
85. Liles, W. C., Kiener, P. A., Ledbetter, J. A., Aruffo, A., Klebanoff, S. J. (1996) Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: implications for the regulation of apoptosis in neutrophils. J. Exp. Med. 184, 429-440.
86. Fecho, K., Bentley, S. A., Cohen, P. L. (1998) Mice deficient in fas ligand (gld) or fas (lpr) show few alterations in granulopoiesis. Cell. Immunol. 188, 19-32.
87. Fecho, K., Cohen, P. L. (1998) Fas ligand (gld)- and Fas (lpr)-deficient mice do not show alterations in the extravasation or apoptosis of inflammatory neutrophils. J. Leukoc. Biol. 64, 373-383.
88. O'Donnell, J. A., Kennedy, C. L., Pellegrini, M., Nowell, C. J., Zhang, J. G., O'Reilly, L. A., Cengia, L., Dias, S., Masters, S. L., Hartland, E. L., Roberts, A. W., Gerlic, M., Croker, B. A. (2015) Fas regulates neutrophil lifespan during viral and bacterial infection. J. Leukoc. Biol. 97, 321-326.
89. Tauzin, S., Debure, L., Moreau, J. F., Legembre, P. (2012) CD95- mediated cell signaling in cancer: mutations and post-translational modulations. Cell. Mol. Life Sci. 69, 1261-1277.
90. Villa-Morales, M., Cobos, M. A., González-Gugel, E., álvarez-Iglesias, V., Martínez, B., Piris, M. A., Carracedo, A., Benítez, J., Fernández-Piqueras, J. (2014) FAS system deregulation in T-cell lymphoblastic lymphoma. Cell Death Dis. 5, e1110.
91. Landowski, T. H., Qu, N., Buyuksal, I., Painter, J. S., Dalton, W. S. (1997) Mutations in the Fas antigen in patients with multiple myeloma. Blood 90, 4266-4270.
92. Mollinedo, F. (2008) Death receptors in multiple myeloma and therapeutic opportunities. In Myeloma Therapy. Pursuing the Plasma Cell (S. Lonial, ed.), Humana Press, Totowa, NJ, 393-419.
93. Shima, Y., Nishimoto, N., Ogata, A., Fujii, Y., Yoshizaki, K., Kishimoto, T. (1995) Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis. Blood 85, 757-764.
94. Westendorf, J. J., Lammert, J. M., Jelinek, D. F. (1995) Expression and function of Fas (APO-1/CD95) in patient myeloma cells and myeloma cell lines. Blood 85, 3566-3576.
95. Landowski, T. H., Shain, K. H., Oshiro, M. M., Buyuksal, I., Painter, J. S., Dalton, W. S. (1999) Myeloma cells selected for resistance to CD95- mediated apoptosis are not cross-resistant to cytotoxic drugs: evidence for independent mechanisms of caspase activation. Blood 94, 265-274.
96. Farre, L., Bittencourt, A. L., Silva-Santos, G., Almeida, A., Silva, A. C., Decanine, D., Soares, G. M., Alcantara, Jr., L. C., Van Dooren, S., Galvão-Castro, B., Vandamme, A. M., Van Weyenbergh, J. (2008) Fas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia. J. Leukoc. Biol. 83, 220-222.
97. Bollain-Y-Goytia, J. J., Arellano-Rodríguez, M., Torres-Del-Muro, Fde. J., Daza-Benítez, L., Muñoz-Valle, J. F., Avalos-Díaz, E., Herrera-Esparza, R. (2014) Soluble fas and the -670 polymorphism of fas in lupus nephritis. Int. J. Nephrol. 2014, 780406.
98. Parlato, S., Giammarioli, A. M., Logozzi, M., Lozupone, F., Matarrese, P., Luciani, F., Falchi, M., Malorni, W., Fais, S. (2000) CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway. EMBO J. 19, 5123-5134.
99. Gajate, C., Mollinedo, F. (2001) The antitumor ether lipid ET-18-OCH3 induces apoptosis through translocation and capping of Fas/CD95 into membrane rafts in human leukemic cells. Blood 98, 3860-3863.
100. Hueber, A. O., Bernard, A. M., Herincs, Z., Couzinet, A., He, H. T. (2002) An essential role for membrane rafts in the initiation of Fas/ CD95-triggered cell death in mouse thymocytes. EMBO Rep. 3, 190-196.
101. Bénéteau, M., Pizon, M., Chaigne-Delalande, B., Daburon, S., Moreau, P., De Giorgi, F., Ichas, F., Rebillard, A., Dimanche-Boitrel, M. T., Taupin, J. L., Moreau, J. F., Legembre, P. (2008) Localization of Fas/ CD95 into the lipid rafts on down-modulation of the phosphatidylinositol 3-kinase signaling pathway. Mol. Cancer Res. 6, 604-613.
102. Stein, R., Mattes, M. J., Cardillo, T. M., Hansen, H. J., Chang, C. H., Burton, J., Govindan, S., Goldenberg, D. M. (2007) CD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clin. Cancer Res. 13, 5556s-5563s.
103. De Totero, D., Tazzari, P. L., Capaia, M., Montera, M. P., Clavio, M., Balleari, E., Foa, R., Gobbi, M. (2003) CD40 triggering enhances fludarabine-induced apoptosis of chronic lymphocytic leukemia B-cells through autocrine release of tumor necrosis factor-alpha and interferon-gama and tumor necrosis factor receptor-I-II upregulation. Haematologica 88, 148-158.
104. Chiantia, S., Ries, J., Chwastek, G., Carrer, D., Li, Z., Bittman, R., Schwille, P. (2008) Role of ceramide in membrane protein organization investigated by combined AFM and FCS. Biochim. Biophys. Acta 1778, 1356-1364.
105. Scheel-Toellner, D., Wang, K., Singh, R., Majeed, S., Raza, K., Curnow, S. J., Salmon, M., Lord, J. M. (2002) The death-inducing signalling complex is recruited to lipid rafts in Fas-induced apoptosis. Biochem. Biophys. Res. Commun. 297, 876-879.
106. Muppidi, J. R., Siegel, R. M. (2004) Ligand-independent redistribution of Fas (CD95) into lipid rafts mediates clonotypic T cell death. Nat. Immunol. 5, 182-189.
107. Mollinedo, F., Gajate, C. (2006) FasL-independent activation of Fas. In Fas Signaling (H. Wajant, ed.), Landes Bioscience and Springer Science, Georgetown, TX, 13-27.
108. Mollinedo, F., Borregaard, N., Boxer, L. A. (1999) Novel trends in neutrophil structure, function and development. Immunol. Today 20, 535-537.
109. Savill, J. S., Wyllie, A. H., Henson, J. E., Walport, M. J., Henson, P. M., Haslett, C. (1989) Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. J. Clin. Invest. 83, 865-875.
110. Haslett, C. (1992) Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes. Clin. Sci. 83, 639-648.
111. Brach, M. A., deVos, S., Gruss, H. J., Herrmann, F. (1992) Prolongation of survival of human polymorphonuclear neutrophils by granulocytemacrophage colony-stimulating factor is caused by inhibition of programmed cell death. Blood 80, 2920-2924.
112. Payne, C. M., Glasser, L., Tischler, M. E., Wyckoff, D., Cromey, D., Fiederlein, R., Bohnert, O. (1994) Programmed cell death of the normal human neutrophil: an in vitro model of senescence. Microsc. Res. Tech. 28, 327-344.
113. Squier, M. K., Sehnert, A. J., Cohen, J. J. (1995) Apoptosis in leukocytes. J. Leukoc. Biol. 57, 2-10.
114. Pitrak, D. L., Tsai, H. C., Mullane, K. M., Sutton, S. H., Stevens, P. (1996) Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome. J. Clin. Invest. 98, 2714-2719.
115. Mollinedo, F., Santos-Beneit, A. M., Gajate, C. (1998) The human leukemia cell line HL-60 as a cell culture model to study neutrophil functions and inflammatory responses. In Animal Cell Culture Techniques (M. Clynes, ed.), Springer-Verlag, Heidelberg, Germany, 264-297.
116. Chilvers, E. R., Cadwallader, K. A., Reed, B. J., White, J. F., Condliffe, A. M. (2000) The function and fate of neutrophils at the inflamed site: prospects for therapeutic intervention. J. R. Coll. Physicians Lond. 34, 68-74.
117. Santos-Beneit, A. M., Mollinedo, F. (2000) Expression of genes involved in initiation, regulation, and execution of apoptosis in human neutrophils and during neutrophil differentiation of HL-60 cells. J. Leukoc. Biol. 67, 712-724.
118. Mollinedo, F., López-Pérez, R., Gajate, C. (2008) Differential gene expression patterns coupled to commitment and acquisition of phenotypic hallmarks during neutrophil differentiation of human leukaemia HL-60 cells. Gene 419, 16-26.
119. Scheel-Toellner, D., Wang, K., Assi, L. K., Webb, P. R., Craddock, R. M., Salmon, M., Lord, J. M. (2004) Clustering of death receptors in lipid rafts initiates neutrophil spontaneous apoptosis. Biochem. Soc. Trans. 32, 679-681.
120. Scheel-Toellner, D., Wang, K., Craddock, R., Webb, P. R., McGettrick, H. M., Assi, L. K., Parkes, N., Clough, L. E., Gulbins, E., Salmon, M., Lord, J. M. (2004) Reactive oxygen species limit neutrophil life span by activating death receptor signaling. Blood 104, 2557-2564.
121. Kasahara, Y., Iwai, K., Yachie, A., Ohta, K., Konno, A., Seki, H., Miyawaki, T., Taniguchi, N. (1997) Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO-1)-mediated apoptosis of neutrophils. Blood 89, 1748-1753.
122. Grassmé, H., Cremesti, A., Kolesnick, R., Gulbins, E. (2003) Ceramidemediated clustering is required for CD95-DISC formation. Oncogene 22, 5457-5470.
123. Grassme, H., Jekle, A., Riehle, A., Schwarz, H., Berger, J., Sandhoff, K., Kolesnick, R., Gulbins, E. (2001) CD95 signaling via ceramide-rich membrane rafts. J. Biol. Chem. 276, 20589-20596.
124. Grassmé, H., Schwarz, H., Gulbins, E. (2001) Molecular mechanisms of ceramide-mediated CD95 clustering. Biochem. Biophys. Res. Commun. 284, 1016-1030.
125. Paris, F., Grassmé, H., Cremesti, A., Zager, J., Fong, Y., Haimovitz- Friedman, A., Fuks, Z., Gulbins, E., Kolesnick, R. (2001) Natural ceramide reverses Fas resistance of acid sphingomyelinase(2/2) hepatocytes. J. Biol. Chem. 276, 8297-8305.
126. Cremesti, A., Paris, F., Grassmé, H., Holler, N., Tschopp, J., Fuks, Z., Gulbins, E., Kolesnick, R. (2001) Ceramide enables fas to cap and kill. J. Biol. Chem. 276, 23954-23961.
127. Kolesnick, R. (2002) The therapeutic potential of modulating the ceramide/sphingomyelin pathway. J. Clin. Invest. 110, 3-8.
128. Edelmann, B., Bertsch, U., Tchikov, V., Winoto-Morbach, S., Perrotta, C., Jakob, M., Adam-Klages, S., Kabelitz, D., Schütze, S. (2011) Caspase-8 and caspase-7 sequentially mediate proteolytic activation of acid sphingomyelinase in TNF-R1 receptosomes. EMBO J. 30, 379-394.
129. Prinetti, A., Chigorno, V., Prioni, S., Loberto, N., Marano, N., Tettamanti, G., Sonnino, S. (2001) Changes in the lipid turnover, composition, and organization, as sphingolipid-enriched membrane domains, in rat cerebellar granule cells developing in vitro. J. Biol. Chem. 276, 21136-21145.
130. Cremesti, A. E., Goni, F. M., Kolesnick, R. (2002) Role of sphingomyelinase and ceramide in modulating rafts: do biophysical properties determine biologic outcome? FEBS Lett. 531, 47-53.
131. Lang, I., Fick, A., Schäfer, V., Giner, T., Siegmund, D., Wajant, H. (2012) Signaling active CD95 receptor molecules trigger cotranslocation of inactive CD95 molecules into lipid rafts. J. Biol. Chem. 287, 24026-24042.
132. Johnston, I., Johnston, L. J. (2006) Ceramide promotes restructuring of model raft membranes. Langmuir 22, 11284-11289.
133. Ira, Johnston, L. J. (2008) Sphingomyelinase generation of ceramide promotes clustering of nanoscale domains in supported bilayer membranes. Biochim. Biophys. Acta 1778, 185-197.
134. Gulbins, E. (2003) Regulation of death receptor signaling and apoptosis by ceramide. Pharmacol. Res. 47, 393-399.
135. Castro, B. M., de Almeida, R. F., Goormaghtigh, E., Fedorov, A., Prieto, M. (2011) Organization and dynamics of Fas transmembrane domain in raft membranes and modulation by ceramide. Biophys. J. 101, 1632-1641.
136. Silva, L. C., de Almeida, R. F., Castro, B. M., Fedorov, A., Prieto, M. (2007) Ceramide-domain formation and collapse in lipid rafts: membrane reorganization by an apoptotic lipid. Biophys. J. 92, 502-516.
137. De Gassart, A., Geminard, C., Fevrier, B., Raposo, G., Vidal, M. (2003) Lipid raft-associated protein sorting in exosomes. Blood 102, 4336-4344.
138. Trajkovic, K., Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., Schwille, P., Br ügger, B., Simons, M. (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319, 1244-1247.
139. Matzke, A., Massing, U., Krug, H. F. (2001) Killing tumour cells by alkylphosphocholines: evidence for involvement of CD95. Eur. J. Cell Biol. 80, 1-10.
140. Gajate, C., Gonzalez-Camacho, F., Mollinedo, F. (2009) Involvement of raft aggregates enriched in Fas/CD95 death-inducing signaling complex in the antileukemic action of edelfosine in Jurkat cells. PLoS One 4, e5044.
141. Gajate, C., Gonzalez-Camacho, F., Mollinedo, F. (2009) Lipid raft connection between extrinsic and intrinsic apoptotic pathways. Biochem. Biophys. Res. Commun. 380, 780-784.
142. Gajate, C., Mollinedo, F. (2007) Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts. Blood 109, 711-719.
143. Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T., Nagata, S. (1993) Lethal effect of the anti-Fas antibody in mice. Nature 364, 806-809.
144. Busto, J. V., Del Canto-Jañez, E., Goñi, F. M., Mollinedo, F., Alonso, A. (2008) Combination of the anti-tumour cell ether lipid edelfosine with sterols abolishes haemolytic side effects of the drug. J. Chem. Biol. 1, 89-94.
145. Ausili, A., Torrecillas, A., Aranda, F. J., Mollinedo, F., Gajate, C., Corbalán-Garćıa, S., de Godos, A., Gómez-Fernández, J. C. (2008) Edelfosine is incorporated into rafts and alters their organization. J. Phys. Chem. B 112, 11643-11654.
146. Cuesta-Marbán, Á., Botet, J., Czyz, O., Cacharro, L. M., Gajate, C., Hornillos, V., Delgado, J., Zhang, H., Amat-Guerri, F., Acuña, A. U., McMaster, C. R., Revuelta, J. L., Zaremberg, V., Mollinedo, F. (2013) Drug uptake, lipid rafts, and vesicle trafficking modulate resistance to an anticancer lysophosphatidylcholine analogue in yeast. J. Biol. Chem. 288, 8405-8418.
147. Van der Luit, A. H., Budde, M., Ruurs, P., Verheij, M., van Blitterswijk, W. J. (2002) Alkyl-lysophospholipid accumulates in lipid rafts and induces apoptosis via raft-dependent endocytosis and inhibition of phosphatidylcholine synthesis. J. Biol. Chem. 277, 39541-39547.
148. Van Der Luit, A. H., Budde, M., Verheij, M., Van Blitterswijk, W. J. (2003) Different modes of internalization of apoptotic alkyllysophospholipid and cell-rescuing lysophosphatidylcholine. Biochem. J. 374, 747-753.
149. Van der Luit, A. H., Vink, S. R., Klarenbeek, J. B., Perrissoud, D., Solary, E., Verheij, M., van Blitterswijk, W. J. (2007) A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells. Mol. Cancer Ther. 6, 2337-2345.
150. Zaremberg, V., Gajate, C., Cacharro, L. M., Mollinedo, F., McMaster, C. R. (2005) Cytotoxicity of an anti-cancer lysophospholipid through selective modification of lipid raft composition. J. Biol. Chem. 280, 38047-38058.
151. Gajate, C., Mollinedo, F. (2005) Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosispromoting clusters in cancer chemotherapy. J. Biol. Chem. 280, 11641-11647.
152. Mollinedo, F., Gajate, C. (2010) Lipid rafts and clusters of apoptotic signaling molecule-enriched rafts in cancer therapy. Future Oncol. 6, 811-821.
153. Mollinedo, F., Gajate, C. (2010) Lipid rafts, death receptors and CASMERs: new insights for cancer therapy. Future Oncol. 6, 491-494.
154. Luo, X., Budihardjo, I., Zou, H., Slaughter, C., Wang, X. (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94, 481-490.
155. Li, H., Zhu, H., Xu, C. J., Yuan, J. (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491-501.
156. Reis-Sobreiro, M., Gajate, C., Mollinedo, F. (2009) Involvement of mitochondria and recruitment of Fas/CD95 signaling in lipid rafts in resveratrol-mediated antimyeloma and antileukemia actions. Oncogene 28, 3221-3234.
157. Mollinedo, F., Fernández, M., Hornillos, V., Delgado, J., Amat-Guerri, F., Acuña, A. U., Nieto-Miguel, T., Villa-Pulgarín, J. A., González-Garćıa, C., Ceña, V., Gajate, C. (2011) Involvement of lipid rafts in the localization and dysfunction effect of the antitumor ether phospholipid edelfosine in mitochondria. Cell Death Dis. 2, e158.
158. Gajate, C., Matos-da-Silva, M., Dakir, H., Fonteriz, R. I., Alvarez, J., Mollinedo, F. (2012) Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum. Oncogene 31, 2627-2639.
159. Gajate, C., Santos-Beneit, A. M., Macho, A., Lazaro, M., Hernandez-De Rojas, A., Modolell, M., Muñoz, E., Mollinedo, F. (2000) Involvement of mitochondria and caspase-3 in ET-18-OCH3-induced apoptosis of human leukemic cells. Int. J. Cancer 86, 208-218.
160. Nieto-Miguel, T., Gajate, C., Mollinedo, F. (2006) Differential targets and subcellular localization of antitumor alkyl-lysophospholipid in leukemic versus solid tumor cells. J. Biol. Chem. 281, 14833- 14840.
161. Garofalo, T., Misasi, R., Mattei, V., Giammarioli, A. M., Malorni, W., Pontieri, G. M., Pavan, A., Sorice, M. (2003) Association of the deathinducing signaling complex with microdomains after triggering through CD95/Fas. Evidence for caspase-8-ganglioside interaction in T cells. J. Biol. Chem. 278, 8309-8315.
162. Sorice, M., Matarrese, P., Tinari, A., Giammarioli, A. M., Garofalo, T., Manganelli, V., Ciarlo, L., Gambardella, L., Maccari, G., Botta, M., Misasi, R., Malorni, W. (2009) Raft component GD3 associates with tubulin following CD95/Fas ligation. FASEB J. 23, 3298-3308.
163. Sorice, M., Matarrese, P., Manganelli, V., Tinari, A., Giammarioli, A. M., Mattei, V., Misasi, R., Garofalo, T., Malorni, W. (2010) Role of GD3- CLIPR-59 association in lymphoblastoid T cell apoptosis triggered by CD95/Fas. PLoS One 5, e8567.
164. Gajate, C., Mollinedo, F. (2015) Lipid rafts and raft-mediated supramolecular entities in the regulation of CD95 death receptor apoptotic signaling. Apoptosis 20, 584-606.
165. Fujinaga, Y., Wolf, A. A., Rodighiero, C., Wheeler, H., Tsai, B., Allen, L., Jobling, M. G., Rapoport, T., Holmes, R. K., Lencer, W. I. (2003) Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to endoplasmic reticulm. Mol. Biol. Cell 14, 4783-4793.
166. Nieto-Miguel, T., Gajate, C., González-Camacho, F., Mollinedo, F. (2008) Proapoptotic role of Hsp90 by its interaction with c-Jun N-terminal kinase in lipid rafts in edelfosine-mediated antileukemic therapy. Oncogene 27, 1779-1787.
167. Whitesell, L., Lindquist, S. L. (2005) HSP90 and the chaperoning of cancer. Nat. Rev. Cancer 5, 761-772.
168. Chen, Y. R., Wang, X., Templeton, D., Davis, R. J., Tan, T. H. (1996) The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. J. Biol. Chem. 271, 31929-31936.
169. Gajate, C., Santos-Beneit, A., Modolell, M., Mollinedo, F. (1998) Involvement of c-Jun NH2-terminal kinase activation and c-Jun in the induction of apoptosis by the ether phospholipid 1-O-octadecyl-2-Omethyl- rac-glycero-3-phosphocholine. Mol. Pharmacol. 53, 602-612.
170. Zhang, H., Wu, W., Du, Y., Santos, S. J., Conrad, S. E., Watson, J. T., Grammatikakis, N., Gallo, K. A. (2004) Hsp90/p50cdc37 is required for mixed-lineage kinase (MLK) 3 signaling. J. Biol. Chem. 279, 19457-19463.
171. Reis-Sobreiro, M., Roué, G., Moros, A., Gajate, C., de la Iglesia-Vicente, J., Colomer, D., Mollinedo, F. (2013) Lipid raft-mediated Akt signaling as a therapeutic target in mantle cell lymphoma. Blood Cancer J. 3, e118.
172. Remacle-Bonnet, M., Garrouste, F., Baillat, G., Andre, F., Marvaldi, J., Pommier, G. (2005) Membrane rafts segregate pro- from anti-apoptotic insulin-like growth factor-I receptor signaling in colon carcinoma cells stimulated by members of the tumor necrosis factor superfamily. Am. J. Pathol. 167, 761-773.
173. Czyz, O., Bitew, T., Cuesta-Marbán, A., McMaster, C. R., Mollinedo, F., Zaremberg, V. (2013) Alteration of plasma membrane organization by an anticancer lysophosphatidylcholine analogue induces intracellular acidification and internalization of plasma membrane transporters in yeast. J. Biol. Chem. 288, 8419-8432.
174. Hanada, M., Feng, J., Hemmings, B. A. (2004) Structure, regulation and function of PKB/AKT-a major therapeutic target. Biochim. Biophys. Acta 1697, 3-16.
175. Scheid, M. P., Woodgett, J. R. (2003) Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Lett. 546, 108-112.
176. Franke, T. F. (2008) PI3K/Akt: getting it right matters. Oncogene 27, 6473-6488.
177. Zoncu, R., Efeyan, A., Sabatini, D. M. (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 12, 21-35.
178. Brazil, D. P., Hemmings, B. A. (2001) Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem. Sci. 26, 657-664.
179. Hill, M. M., Feng, J., Hemmings, B. A. (2002) Identification of a plasma membrane Raft-associated PKB Ser473 kinase activity that is distinct from ILK and PDK1. Curr. Biol. 12, 1251-1255.
180. Park, S. G., Long, M., Kang, J. A., Kim, W. S., Lee, C. R., Im, S. H., Strickland, I., Schulze-Luehrmann, J., Hayden, M. S., Ghosh, S. (2013) The kinase PDK1 is essential for B-cell receptor mediated survival signaling. PLoS One 8, e55378.
181. Lasserre, R., Guo, X. J., Conchonaud, F., Hamon, Y., Hawchar, O., Bernard, A. M., Soudja, S. M., Lenne, P. F., Rigneault, H., Olive, D., Bismuth, G., Nunès, J. A., Payrastre, B., Marguet, D., He, H. T. (2008) Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nat. Chem. Biol. 4, 538-547.
182. Remijsen, Q., Vanden Berghe, T., Parthoens, E., Asselbergh, B., Vandenabeele, P., Willems, J. (2009) Inhibition of spontaneous neutrophil apoptosis by parabutoporin acts independently of NADPH oxidase inhibition but by lipid raft-dependent stimulation of Akt. J. Leukoc. Biol. 85, 497-507.
183. Chakrabandhu, K., Hérincs, Z., Huault, S., Dost, B., Peng, L., Conchonaud, F., Marguet, D., He, H. T., Hueber, A. O. (2007) Palmitoylation is required for efficient Fas cell death signaling. EMBO J. 26, 209-220.
184. Rossin, A., Kral, R., Lounnas, N., Chakrabandhu, K., Mailfert, S., Marguet, D., Hueber, A. O. (2010) Identification of a lysine-rich region of Fas as a raft nanodomain targeting signal necessary for Fas-mediated cell death. Exp. Cell Res. 316, 1513-1522.
185. Freeburn, R. W., Wright, K. L., Burgess, S. J., Astoul, E., Cantrell, D. A., Ward, S. G. (2002) Evidence that SHIP-1 contributes to phosphatidylinositol 3,4,5-trisphosphate metabolism in T lymphocytes and can regulate novel phosphoinositide 3-kinase effectors. J. Immunol. 169, 5441-5450.
186. Kondapaka, S. B., Singh, S. S., Dasmahapatra, G. P., Sausville, E. A., Roy, K. K. (2003) Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. Mol. Cancer Ther. 2, 1093-1103.
187. Varadhachary, A. S., Edidin, M., Hanlon, A. M., Peter, M. E., Krammer, P. H., Salgame, P. (2001) Phosphatidylinositol 39-kinase blocks CD95 aggregation and caspase-8 cleavage at the death-inducing signaling complex by modulating lateral diffusion of CD95. J. Immunol. 166, 6564-6569.
188. Chiarini, F., Del Sole, M., Mongiorgi, S., Gaboardi, G. C., Cappellini, A., Mantovani, I., Follo, M. Y., McCubrey, J. A., Martelli, A. M. (2008) The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute leukemia cells by a JNK-dependent mechanism. Leukemia 22, 1106-1116.
189. Greaves, J., Chamberlain, L. H. (2007) Palmitoylation-dependent protein sorting. J. Cell Biol. 176, 249-254.
190. Levental, I., Lingwood, D., Grzybek, M., Coskun, U., Simons, K. (2010) Palmitoylation regulates raft affinity for the majority of integral raft proteins. Proc. Natl. Acad. Sci. USA 107, 22050-22054.
191. Aicart-Ramos, C., Valero, R. A., Rodriguez-Crespo, I. (2011) Protein palmitoylation and subcellular trafficking. Biochim. Biophys. Acta 1808, 2981-2994.
192. Rossin, A., Durivault, J., Chakhtoura-Feghali, T., Lounnas, N., Gagnoux- Palacios, L., Hueber, A. O. (2015) Fas palmitoylation by the palmitoyl acyltransferase DHHC7 regulates Fas stability. Cell Death Differ. 22, 643-653.
193. Feig, C., Tchikov, V., Schütze, S., Peter, M. E. (2007) Palmitoylation of CD95 facilitates formation of SDS-stable receptor aggregates that initiate apoptosis signaling. EMBO J. 26, 221-231.
194. Kamitani, T., Nguyen, H. P., Yeh, E. T. (1997) Activation-induced aggregation and processing of the human Fas antigen. Detection with cytoplasmic domain-specific antibodies. J. Biol. Chem. 272, 22307-22314.
195. Hawash, I. Y., Hu, X. E., Adal, A., Cassady, J. M., Geahlen, R. L., Harrison, M. L. (2002) The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck localization to lipid rafts and T cell signaling. Biochim. Biophys. Acta 1589, 140-150.
196. Lee, K. H., Feig, C., Tchikov, V., Schickel, R., Hallas, C., Schütze, S., Peter, M. E., Chan, A. C. (2006) The role of receptor internalization in CD95 signaling. EMBO J. 25, 1009-1023.
197. Leon-Bollotte, L., Subramaniam, S., Cauvard, O., Plenchette-Colas, S., Paul, C., Godard, C., Martinez-Ruiz, A., Legembre, P., Jeannin, J. F., Bettaieb, A. (2011) S-Nitrosylation of the death receptor fas promotes fas ligand-mediated apoptosis in cancer cells. Gastroenterology 140, 2009-2018, 2018.e1-4.
198. Cahuzac, N., Baum, W., Kirkin, V., Conchonaud, F., Wawrezinieck, L., Marguet, D., Janssen, O., Zörnig, M., Hueber, A. O. (2006) Fas ligand is localized to membrane rafts, where it displays increased cell deathinducing activity. Blood 107, 2384-2391.
199. Guardiola-Serrano, F., Rossin, A., Cahuzac, N., Lückerath, K., Melzer, I., Mailfert, S., Marguet, D., Zörnig, M., Hueber, A. O. (2010) Palmitoylation of human FasL modulates its cell death-inducing function. Cell Death Dis. 1, e88.
200. Lacour, S., Hammann, A., Grazide, S., Lagadic-Gossmann, D., Athias, A., Sergent, O., Laurent, G., Gambert, P., Solary, E., Dimanche-Boitrel, M. T. (2004) Cisplatin-induced CD95 redistribution into membrane lipid rafts of HT29 human colon cancer cells. Cancer Res. 64, 3593-3598.
201. Delmas, D., Rébé, C., Lacour, S., Filomenko, R., Athias, A., Gambert, P., Cherkaoui-Malki, M., Jannin, B., Dubrez-Daloz, L., Latruffe, N., Solary, E. (2003) Resveratrol-induced apoptosis is associated with Fas redistribution in the rafts and the formation of a death-inducing signaling complex in colon cancer cells. J. Biol. Chem. 278, 41482-41490.
202. Stel, A. J., Ten Cate, B., Jacobs, S., Kok, J. W., Spierings, D. C., Dondorff, M., Helfrich, W., Kluin-Nelemans, H. C., de Leij, L. F., Withoff, S., Kroesen, B. J. (2007) Fas receptor clustering and involvement of the death receptor pathway in rituximab-mediated apoptosis with concomitant sensitization of lymphoma B cells to fas-induced apoptosis. J. Immunol. 178, 2287-2295.
203. Xu, Z. X., Ding, T., Haridas, V., Connolly, F., Gutterman, J. U. (2009) Avicin D, a plant triterpenoid, induces cell apoptosis by recruitment of Fas and downstream signaling molecules into lipid rafts. PLoS One 4, e8532.
204. Bodmer, J. L., Holler, N., Reynard, S., Vinciguerra, P., Schneider, P., Juo, P., Blenis, J., Tschopp, J. (2000) TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat. Cell Biol. 2, 241-243.
205. Kischkel, F. C., Lawrence, D. A., Chuntharapai, A., Schow, P., Kim, K. J., Ashkenazi, A. (2000) Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12, 611-620.
206. Sprick, M. R., Weigand, M. A., Rieser, E., Rauch, C. T., Juo, P., Blenis, J., Krammer, P. H., Walczak, H. (2000) FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity 12, 599-609.
207. Delmas, D., Rébé, C., Micheau, O., Athias, A., Gambert, P., Grazide, S., Laurent, G., Latruffe, N., Solary, E. (2004) Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic toxicity of resveratrol and death receptor ligands in colon carcinoma cells. Oncogene 23, 8979-8986.
208. Gajate, C., Mollinedo, F. (2011) Lipid rafts and Fas/CD95 signaling in cancer chemotherapy. Recent Patents Anticancer. Drug Discov. 6, 274-283.
209. Mollinedo, F., de la Iglesia-Vicente, J., Gajate, C., Estella-Hermoso de Mendoza, A., Villa-Pulgarin, J. A., de Frias, M., Roué, G., Gil, J., Colomer, D., Campanero, M. A., Blanco-Prieto, M. J. (2010) In vitro and In vivo selective antitumor activity of Edelfosine against mantle cell lymphoma and chronic lymphocytic leukemia involving lipid rafts. Clin. Cancer Res. 16, 2046-2054.
210. Lemke, J., von Karstedt, S., Zinngrebe, J., Walczak, H. (2014) Getting TRAIL back on track for cancer therapy. Cell Death Differ. 21, 1350-1364.
211. Mitsiades, C. S., Treon, S. P., Mitsiades, N., Shima, Y., Richardson, P., Schlossman, R., Hideshima, T., Anderson, K. C. (2001) TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma: therapeutic applications. Blood 98, 795-804.
212. Kuehl, W. M., Bergsagel, P. L. (2002) Multiple myeloma: evolving genetic events and host interactions. Nat. Rev. Cancer 2, 175-187.
213. Bruno, B., Giaccone, L., Rotta, M., Anderson, K., Boccadoro, M. (2005) Novel targeted drugs for the treatment of multiple myeloma: from bench to bedside. Leukemia 19, 1729-1738.
214. Berdel, W. E., Bausert, W. R., Fink, U., Rastetter, J., Munder, P. G. (1981) Anti-tumor action of alkyl-lysophospholipids (Review). Anticancer Res. 1, 345-352.
215. Glasser, L., Dalton, W. S., Fiederlein, R. L., Cook, P., Powis, G., Vogler, W. R. (1996) Response of human multiple myeloma-derived cell lines to alkyl-lysophospholipid. Exp. Hematol. 24, 253-257.
216. Hideshima, T., Catley, L., Yasui, H., Ishitsuka, K., Raje, N., Mitsiades, C., Podar, K., Munshi, N. C., Chauhan, D., Richardson, P. G., Anderson, K. C. (2006) Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. Blood 107, 4053-4062.
217. Valdez, B. C., Zander, A. R., Song, G., Murray, D., Nieto, Y., Li, Y., Champlin, R. E., Andersson, B. S. (2014) Synergistic cytotoxicity of gemcitabine, clofarabine and edelfosine in lymphoma cell lines. Blood Cancer J. 4, e171.
218. Ruiter, G. A., Zerp, S. F., Bartelink, H., van Blitterswijk, W. J., Verheij, M. (2003) Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt/PKB survival pathway. Anticancer Drugs 14, 167-173.
219. Gills, J. J., Dennis, P. A. (2009) Perifosine: update on a novel Akt inhibitor. Curr. Oncol. Rep. 11, 102-110.
220. Freeman, M. R., Di Vizio, D., Solomon, K. R. (2010) The Rafts of the Medusa: cholesterol targeting in cancer therapy. Oncogene 29, 3745-3747.
221. Otten, H. G., van Ginkel, W. G., Hagenbeek, A., Petersen, E. J. (2004) Prevalence and clinical significance of resistance to perforin- and FASmediated cell death in leukemia. Leukemia 18, 1401-1405.
222. Moriyama, H., Yonehara, S. (2007) Rapid up-regulation of c-FLIP expression by BCR signaling through the PI3K/Akt pathway inhibits simultaneously induced Fas-mediated apoptosis in murine B lymphocytes. Immunol. Lett. 109, 36-46.
223. Kater, A. P., Dicker, F., Mangiola, M., Welsh, K., Houghten, R., Ostresh, J., Nefzi, A., Reed, J. C., Pinilla, C., Kipps, T. J. (2005) Inhibitors of XIAP sensitize CD40-activated chronic lymphocytic leukemia cells to CD95- mediated apoptosis. Blood 106, 1742-1748.
224. Droin, N., Guéry, L., Benikhlef, N., Solary, E. (2013) Targeting apoptosis proteins in hematological malignancies. Cancer Lett. 332, 325-334.
225. Jones, D. T., Ganeshaguru, K., Virchis, A. E., Folarin, N. I., Lowdell, M. W., Mehta, A. B., Prentice, H. G., Hoffbrand, A. V., Wickremasinghe, R. G. (2001) Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation. Blood 98, 2800-2807.
226. Berkova, Z., Tao, R. H., Samaniego, F. (2010) Milatuzumab-a promising new immunotherapeutic agent. Expert Opin. Investig. Drugs 19, 141-149.
227. Kaufman, J. L., Niesvizky, R., Stadtmauer, E. A., Chanan-Khan, A., Siegel, D., Horne, H., Wegener, W. A., Goldenberg, D. M. (2013) Phase I, multicentre, dose-escalation trial of monotherapy with milatuzumab (humanized anti-CD74 monoclonal antibody) in relapsed or refractory multiple myeloma. Br. J. Haematol. 163, 478-486.
228. Friesen, C., Herr, I., Krammer, P. H., Debatin, K. M. (1996) Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat. Med. 2, 574-577.
229. Friesen, C., Fulda, S., Debatin, K. M. (1999) Cytotoxic drugs and the CD95 pathway. Leukemia 13, 1854-1858.
230. Poulaki, V., Mitsiades, C. S., Mitsiades, N. (2001) The role of Fas and FasL as mediators of anticancer chemotherapy. Drug Resist. Updat. 4, 233-242.
231. Sheard, M. A. (2001) Ionizing radiation as a response-enhancing agent for CD95-mediated apoptosis. Int. J. Cancer 96, 213-220.
232. Eichhorst, S. T., Müerköster, S., Weigand, M. A., Krammer, P. H. (2001) The chemotherapeutic drug 5-fluorouracil induces apoptosis in mouse thymocytes in vivo via activation of the CD95(APO-1/Fas) system. Cancer Res. 61, 243-248.
233. Micheau, O., Solary, E., Hammann, A., Dimanche-Boitrel, M. T. (1999) Fas ligand-independent, FADD-mediated activation of the Fas death pathway by anticancer drugs. J. Biol. Chem. 274, 7987-7992.
234. Eramo, A., Sargiacomo, M., Ricci-Vitiani, L., Todaro, M., Stassi, G., Messina, C. G., Parolini, I., Lotti, F., Sette, G., Peschle, C., De Maria, R. (2004) CD95 death-inducing signaling complex formation and internalization occur in lipid rafts of type I and type II cells. Eur. J. Immunol. 34, 1930-1940.
235. Pizon, M., Rampanarivo, H., Tauzin, S., Chaigne-Delalande, B., Daburon, S., Castroviejo, M., Moreau, P., Moreau, J. F., Legembre, P. (2011) Actin-independent exclusion of CD95 by PI3K/AKT signalling: implications for apoptosis. Eur. J. Immunol. 41, 2368-2378.
236. Moretti, S., Procopio, A., Lazzarini, R., Rippo, M. R., Testa, R., Marra, M., Tamagnone, L., Catalano, A. (2008) Semaphorin3A signaling controls Fas (CD95)-mediated apoptosis by promoting Fas translocation into lipid rafts. Blood 111, 2290-2299.
237. Oberle, C., Massing, U., Krug, H. F. (2005) On the mechanism of alkylphosphocholine (APC)-induced apoptosis in tumour cells. Biol. Chem. 386, 237-245.
238. Andreesen, R., Modolell, M., Weltzien, H. U., Munder, P. G. (1980) Alkyl-lysophospholipid induced suppression of human lymphocyte response to mitogens and selective killing of lymphoblasts. Immunobiology 156, 498-508.
239. Cabaner, C., Gajate, C., Macho, A., Muñoz, E., Modolell, M., Mollinedo, F. (1999) Induction of apoptosis in human mitogen-activated peripheral blood T-lymphocytes by the ether phospholipid ET-18-OCH3: involvement of the Fas receptor/ligand system. Br. J. Pharmacol. 127, 813-825.
240. Hanson, P. K., Malone, L., Birchmore, J. L., Nichols, J. W. (2003) Lem3p is essential for the uptake and potency of alkylphosphocholine drugs, edelfosine and miltefosine. J. Biol. Chem. 278, 36041-36050.
241. Pérez-Victoria, F. J., Gamarro, F., Ouellette, M., Castanys, S. (2003) Functional cloning of the miltefosine transporter. A novel P-type phospholipid translocase from Leishmania involved in drug resistance. J. Biol. Chem. 278, 49965-49971.
242. Chen, R., Brady, E., McIntyre, T. M. (2011) Human TMEM30a promotes uptake of antitumor and bioactive choline phospholipids into mammalian cells. J. Immunol. 186, 3215-3225.
243. Muñoz-Martínez, F., Torres, C., Castanys, S., Gamarro, F. (2010) CDC50A plays a key role in the uptake of the anticancer drug perifosine in human carcinoma cells. Biochem. Pharmacol. 80, 793-800.
244. Mollinedo, F., Martínez-Dalmau, R., Modolell, M. (1993) Early and selective induction of apoptosis in human leukemic cells by the alkyllysophospholipid ET-18-OCH3. Biochem. Biophys. Res. Commun. 192, 603-609.
245. Sospedra, M., Martin, R. (2005) Immunology of multiple sclerosis. Annu. Rev. Immunol. 23, 683-747.
246. Compston, A., Coles, A. (2008) Multiple sclerosis. Lancet 372, 1502-1517.
247. Owens, T., Sriram, S. (1995) The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis. Neurol. Clin. 13, 51-73.
248. Skundric, D. S. (2005) Experimental models of relapsing-remitting multiple sclerosis: current concepts and perspective. Curr. Neurovasc. Res. 2, 349-362.
249. Engelhardt, B., Diamantstein, T., Wekerle, H. (1989) Immunotherapy of experimental autoimmune encephalomyelitis (EAE): differential effect of anti-IL-2 receptor antibody therapy on actively induced and T-line mediated EAE of the Lewis rat. J. Autoimmun. 2, 61-73.
250. Baker, D., O'Neill, J. K., Amor, S., Khamashta, M. A., Turk, J. L. (1991) Inhibition of chronic relapsing experimental allergic encephalomyelitis in the mouse by the alkyl-lysophospholipid ET-18-OCH3. Int. J. Immunopharmacol. 13, 385-392.
251. Chabannes, D., Ryffel, B., Borel, J. F. (1992) SRI 62-834, a cyclic ether analogue of the phospholipid ET-18-OCH3, displays long-lasting beneficial effect in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. Comparison with cyclosporin and (Val2)-dihydrocyclosporin effects in clinical, functional and histological studies. J. Autoimmun. 5, 199-211.
252. Klein-Franke, A., Munder, P. G. (1992) Alkyllysophospholipid prevents induction of experimental allergic encephalomyelitis. J. Autoimmun. 5, 83-91.
253. Kovarik, J., Chabannes, D., Borel, J. F. (1995) Immunoregulation and drug treatment in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. Int. J. Immunopharmacol. 17, 255-263.
254. Abramowski, P., Otto, B., Martin, R. (2014) The orally available, synthetic ether lipid edelfosine inhibits T cell proliferation and induces a type I interferon response. PLoS One 9, e91970.
255. Abramowski, P., Steinbach, K., Zander, A. R., Martin, R. (2014) Immunomodulatory effects of the ether phospholipid edelfosine in experimental autoimmune encephalomyelitis. J. Neuroimmunol. 274, 111-124.
256. Munder, P. G., Westphal, O. (1990) Antitumoral and other biomedical activities of synthetic ether lysophospholipids. Chem. Immunol. 49, 206-235.
257. Wajant, H., Pfizenmaier, K., Scheurich, P. (2003) Non-apoptotic Fas signaling. Cytokine Growth Factor Rev. 14, 53-66.
258. Park, S. M., Schickel, R., Peter, M. E. (2005) Nonapoptotic functions of FADD-binding death receptors and their signaling molecules. Curr. Opin. Cell Biol. 17, 610-616.
259. Brint, E., O'Callaghan, G., Houston, A. (2013) Life in the Fas lane: differential outcomes of Fas signaling. Cell. Mol. Life Sci. 70, 4085-4099.
260. Legembre, P., Barnhart, B. C., Peter, M. E. (2004) The relevance of NFkappaB for CD95 signaling in tumor cells. Cell Cycle 3, 1235-1239.
261. Maksimow, M., Söderström, T. S., Jalkanen, S., Eriksson, J. E., Hänninen, A. (2006) Fas costimulation of naive CD4 T cells is controlled by NF-kappaB signaling and caspase activity. J. Leukoc. Biol. 79, 369-377.
262. Kreuz, S., Siegmund, D., Rumpf, J. J., Samel, D., Leverkus, M., Janssen, O., Häcker, G., Dittrich-Breiholz, O., Kracht, M., Scheurich, P., Wajant, H. (2004) NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP. J. Cell Biol. 166, 369-380.
263. Peter, M. E., Budd, R. C., Desbarats, J., Hedrick, S. M., Hueber, A. O., Newell, M. K., Owen, L. B., Pope, R. M., Tschopp, J., Wajant, H., Wallach, D., Wiltrout, R. H., Zörnig, M., Lynch, D. H. (2007) The CD95 receptor: apoptosis revisited. Cell 129, 447-450.
264. Kleber, S., Sancho-Martinez, I., Wiestler, B., Beisel, A., Gieffers, C., Hill, O., Thiemann, M., Mueller, W., Sykora, J., Kuhn, A., Schreglmann, N., Letellier, E., Zuliani, C., Klussmann, S., Teodorczyk, M., Gröne, H. J., Ganten, T. M., Sültmann, H., Tüttenberg, J., von Deimling, A., Regnier- Vigouroux, A., Herold-Mende, C., Martin-Villalba, A. (2008) Yes and PI3K bind CD95 to signal invasion of glioblastoma. Cancer Cell 13, 235-248.
265. Letellier, E., Kumar, S., Sancho-Martinez, I., Krauth, S., Funke-Kaiser, A., Laudenklos, S., Konecki, K., Klussmann, S., Corsini, N. S., Kleber, S., Drost, N., Neumann, A., Lévi-Strauss, M., Brors, B., Gretz, N., Edler, L., Fischer, C., Hill, O., Thiemann, M., Biglari, B., Karray, S., Martin- Villalba, A. (2010) CD95-ligand on peripheral myeloid cells activates Syk kinase to trigger their recruitment to the inflammatory site. Immunity 32, 240-252.
266. Kober, A. M., Legewie, S., Pforr, C., Fricker, N., Eils, R., Krammer, P. H., Lavrik, I. N. (2011) Caspase-8 activity has an essential role in CD95/Fasmediated MAPK activation. Cell Death Dis. 2, e212.
267. Martin-Villalba, A., Llorens-Bobadilla, E., Wollny, D. (2013) CD95 in cancer: tool or target? Trends Mol. Med. 19, 329-335.
268. Song, J. H., Tse, M. C., Bellail, A., Phuphanich, S., Khuri, F., Kneteman, N. M., Hao, C. (2007) Lipid rafts and nonrafts mediate tumor necrosis factor related apoptosis-inducing ligand induced apoptotic and nonapoptotic signals in non small cell lung carcinoma cells. Cancer Res. 67, 6946-6955.
269. Doan, J. E., Windmiller, D. A., Riches, D. W. (2004) Differential regulation of TNF-R1 signaling: lipid raft dependency of p42mapk/erk2 activation, but not NF-kappaB activation. J. Immunol. 172, 7654-7660.
270. Young, R. M., Holowka, D., Baird, B. (2003) A lipid raft environment enhances Lyn kinase activity by protecting the active site tyrosine from dephosphorylation. J. Biol. Chem. 278, 20746-20752.
271. Hughes, M. A., Harper, N., Butterworth, M., Cain, K., Cohen, G. M., MacFarlane, M. (2009) Reconstitution of the death-inducing signaling complex reveals a substrate switch that determines CD95-mediated death or survival. Mol. Cell 35, 265-279.
272. Melo-Lima, S., Lopes, M. C., Mollinedo, F. (2015) ERK1/2 acts as a switch between necrotic and apoptotic cell death in ether phospholipid edelfosine-treated glioblastoma cells. Pharmacol. Res. 95-96, 2-11.
273. Melo-Lima, S., Gajate, C., Mollinedo, F. (2015) Triggers and signaling cross-talk controlling cell death commitment. Cell Cycle 14, 465-466.
274. Ciarlo, L., Manganelli, V., Garofalo, T., Matarrese, P., Tinari, A., Misasi, R., Malorni, W., Sorice, M. (2010) Association of fission proteins with mitochondrial raft-like domains. Cell Death Differ. 17, 1047-1058.
275. Sorice, M., Manganelli, V., Matarrese, P., Tinari, A., Misasi, R., Malorni, W., Garofalo, T. (2009) Cardiolipin-enriched raft-like microdomains are essential activating platforms for apoptotic signals on mitochondria. FEBS Lett. 583, 2447-2450.
276. Belzil, V. V., Rouleau, G. A. (2012) Endoplasmic reticulum lipid rafts and upper motor neuron degeneration. Ann. Neurol. 72, 479-480.
277. Boslem, E., Weir, J. M., MacIntosh, G., Sue, N., Cantley, J., Meikle, P. J., Biden, T. J. (2013) Alteration of endoplasmic reticulum lipid rafts contributes to lipotoxicity in pancreatic b-cells. J. Biol. Chem. 288, 26569-26582.
278. Kornmann, B., Walter, P. (2010) ERMES-mediated ER-mitochondria contacts: molecular hubs for the regulation of mitochondrial biology. J. Cell Sci. 123, 1389-1393.
279. Annunziata, I., Patterson, A., d'Azzo, A. (2013) Mitochondria-associated ER membranes (MAMs) and glycosphingolipid enriched microdomains (GEMs): isolation from mouse brain. J. Vis. Exp. 4, e50215.
280. Mollinedo, F., Gajate, C., Morales, A. I., del Canto-Jañez, E., Justies, N., Collía, F., Rivas, J. V., Modolell, M., Iglesias, A. (2009) Novel antiinflammatory action of edelfosine lacking toxicity with protective effect in experimental colitis. J. Pharmacol. Exp. Ther. 329, 439-449.