|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 280, Issue 12, 11641-11647, March 25, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cytoskeleton-mediated Death Receptor and Ligand Concentration in Lipid Rafts Forms Apoptosis-promoting Clusters in Cancer Chemotherapy*
From the Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain
While investigating the mechanism of action of the novel antitumor drug Aplidin, we have discovered a potent and novel cell-killing mechanism that involves the formation of Fas/CD95-driven scaffolds in membrane raft clusters housing death receptors and apoptosis-related molecules. Fas, tumor necrosis factor-receptor 1, and tumor necrosis factor-related apoptosis-inducing ligand receptor 2/death receptor 5 were clustered into lipid rafts in leukemic Jurkat cells following Aplidin treatment, the presence of Fas being essential for apoptosis. Preformed membrane-bound Fas ligand (FasL) as well as downstream signaling molecules, including Fas-associated death domain-containing protein, procaspase-8, procaspase-10, c-Jun amino-terminal kinase, and Bid, were also translocated into lipid rafts, connecting death receptor extrinsic and mitochondrial intrinsic apoptotic pathways. Blocking Fas/FasL interaction partially inhibited Aplidin-induced apoptosis. Aplidin was rapidly incorporated into membrane rafts, and drug uptake was inhibited by lipid raft disruption. Actin-linking proteins ezrin, moesin, RhoA, and RhoGDI were conveyed into Fas-enriched rafts in drug-treated leukemic cells. Disruption of lipid rafts and interference with actin cytoskeleton prevented Fas clustering and apoptosis. Thus, Aplidin-induced apoptosis involves Fas activation in both a FasL-independent way and, following Fas/FasL interaction, an autocrine way through the concentration of Fas, membrane-bound FasL, and signaling molecules in membrane rafts. These data indicate a major role of actin cytoskeleton in the formation of Fas caps and highlight the crucial role of the clusters of apoptotic signaling molecule-enriched rafts in apoptosis, acting as concentrators of death receptors and downstream signaling molecules and as the linchpin from which a potent death signal is launched.
Received for publication, October 18, 2004 , and in revised form, January 3, 2005.
* This work was supported by Fondo de Investigación Sanitaria Grants FIS04/0843 and FIS02/1199. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 34-923-294806; Fax: 34-923-294795; E-mail: fmollin{at}usal.es.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. S. Mitsiades, E. M. Ocio, A. Pandiella, P. Maiso, C. Gajate, M. Garayoa, D. Vilanova, J. C. Montero, N. Mitsiades, C. J. McMullan, et al. Aplidin, a Marine Organism-Derived Compound with Potent Antimyeloma Activity In vitro and In vivo Cancer Res., July 1, 2008; 68(13): 5216 - 5225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mikhailov, A. Sokolovskaya, G. G. Yegutkin, H. Amdahl, A. West, H. Yagita, R. Lahesmaa, L. F. Thompson, S. Jalkanen, D. Blokhin, et al. CD73 Participates in Cellular Multiresistance Program and Protects against TRAIL-Induced Apoptosis J. Immunol., July 1, 2008; 181(1): 464 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Beneteau, M. Pizon, B. Chaigne-Delalande, S. Daburon, P. Moreau, F. De Giorgi, F. Ichas, A. Rebillard, M.-T. Dimanche-Boitrel, J.-L. Taupin, et al. Localization of Fas/CD95 into the Lipid Rafts on Down-Modulation of the Phosphatidylinositol 3-Kinase Signaling Pathway Mol. Cancer Res., April 1, 2008; 6(4): 604 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Munoz-Alonso, L. Gonzalez-Santiago, N. Zarich, T. Martinez, E. Alvarez, J. M. Rojas, and A. Munoz Plitidepsin Has a Dual Effect Inhibiting Cell Cycle and Inducing Apoptosis via Rac1/c-Jun NH2-Terminal Kinase Activation in Human Melanoma Cells J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1093 - 1101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Moretti, A. Procopio, R. Lazzarini, M. R. Rippo, R. Testa, M. Marra, L. Tamagnone, and A. Catalano Semaphorin3A signaling controls Fas (CD95)-mediated apoptosis by promoting Fas translocation into lipid rafts Blood, February 15, 2008; 111(4): 2290 - 2299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sharif-Askari, D. Gaucher, R. Halwani, J. Ma, K. Jao, A. Abdallah, E. K. Haddad, and R.-P. Sekaly p56Lck Tyrosine Kinase Enhances the Assembly of Death-inducing Signaling Complex during Fas-mediated Apoptosis J. Biol. Chem., December 7, 2007; 282(49): 36048 - 36056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Park, K. Teja, J. J. O'Shea, and R. M. Siegel The Yersinia Effector Protein YpkA Induces Apoptosis Independently of Actin Depolymerization J. Immunol., May 15, 2007; 178(10): 6426 - 6434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. DeMorrow, S. Glaser, H. Francis, J. Venter, B. Vaculin, S. Vaculin, and G. Alpini Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth: RECRUITMENT OF Fas AND Fas LIGAND TO LIPID RAFTS J. Biol. Chem., April 27, 2007; 282(17): 13098 - 13113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gajate and F. Mollinedo Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts Blood, January 15, 2007; 109(2): 711 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Hunter and G. F. Nixon Spatial Compartmentalization of Tumor Necrosis Factor (TNF) Receptor 1-dependent Signaling Pathways in Human Airway Smooth Muscle Cells: LIPID RAFTS ARE ESSENTIAL FOR TNF-{alpha}-MEDIATED ACTIVATION OF RhoA BUT DISPENSABLE FOR THE ACTIVATION OF THE NF-{kappa}B AND MAPK PATHWAYS J. Biol. Chem., November 10, 2006; 281(45): 34705 - 34715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Suarez, L. Gonzalez-Santiago, N. Zarich, A. Davalos, J. F. Aranda, M. A. Alonso, M. A. Lasuncion, J. M. Rojas, and A. Munoz Plitidepsin Cellular Binding and Rac1/JNK Pathway Activation Depend on Membrane Cholesterol Content Mol. Pharmacol., November 1, 2006; 70(5): 1654 - 1663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bari, P. Spagnuolo, F. Fezza, S. Oddi, N. Pasquariello, A. Finazzi-Agro, and M. Maccarrone Effect of Lipid Rafts on Cb2 Receptor Signaling and 2-Arachidonoyl-Glycerol Metabolism in Human Immune Cells J. Immunol., October 15, 2006; 177(8): 4971 - 4980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nieto-Miguel, C. Gajate, and F. Mollinedo Differential Targets and Subcellular Localization of Antitumor Alkyl-lysophospholipid in Leukemic Versus Solid Tumor Cells J. Biol. Chem., May 26, 2006; 281(21): 14833 - 14840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-L. Hsiao, W.-S. Wang, P.-M. Chen, and Y. Su Overexpression of thymosin {beta}-4 renders SW480 colon carcinoma cells more resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via downregulating Fas and upregulating Survivin expression, respectively Carcinogenesis, May 1, 2006; 27(5): 936 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Nachbur, D. Kassahn, S. Yousefi, D. F. Legler, and T. Brunner Posttranscriptional regulation of Fas (CD95) ligand killing activity by lipid rafts Blood, April 1, 2006; 107(7): 2790 - 2796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Cahuzac, W. Baum, V. Kirkin, F. Conchonaud, L. Wawrezinieck, D. Marguet, O. Janssen, M. Zornig, and A.-O. Hueber Fas ligand is localized to membrane rafts, where it displays increased cell death-inducing activity Blood, March 15, 2006; 107(6): 2384 - 2391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yu, E. Davicioni, T. J. Triche, and G. Merlino The Homeoprotein Six1 Transcriptionally Activates Multiple Protumorigenic Genes but Requires Ezrin to Promote Metastasis Cancer Res., February 15, 2006; 66(4): 1982 - 1989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Abouzahr, G. Bismuth, C. Gaudin, O. Caroll, P. Van Endert, A. Jalil, J. Dausset, I. Vergnon, C. Richon, A. Kauffmann, et al. Identification of target actin content and polymerization status as a mechanism of tumor resistance after cytolytic T lymphocyte pressure PNAS, January 31, 2006; 103(5): 1428 - 1433. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |