2024-03-28T12:45:47Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/610152020-09-30T12:12:06Zcom_10261_112com_10261_1col_10261_365
00925njm 22002777a 4500
dc
Gajate, Consuelo
author
González-Camacho, Fernando
author
Mollinedo, Faustino
author
2009
Apoptosis in mammalian cells is modulated by extrinsic and intrinsic signaling pathways through the formation of death receptor-mediated death-inducing signaling complex (DISC) and mitochondrial-derived apoptosome, respectively. We found by ultrastructural approaches that the antitumor drug edelfosine induced aggregates of lipid rafts containing Fas/CD95 receptor and Fas-associated death domain-containing protein in leukemic cells. Death receptors together with DISC and apoptosome constituents were recruited in rafts during edelfosine treatment in multiple myeloma cells. This apoptotic response involved caspases-8/-9/-10 that were translocated to rafts. Lipid raft disruption by cholesterol depletion inhibited loss of mitochondrial transmembrane potential, caspase activation and apoptosis, whereas cholesterol replenishment restored these responses. Our data indicate that rafts act as scaffolds where extrinsic and intrinsic apoptotic signaling pathways concentrate, forming clusters of apoptotic signaling molecule-enriched rafts (CASMER), which function as novel supramolecular entities in the triggering of apoptosis, and play an important role in edelfosine-induced apoptosis in blood cancer cells.
Biochemical and Biophysical Research Communications 380(4): 780-784 (2009)
http://hdl.handle.net/10261/61015
10.1016/j.bbrc.2009.01.147
Lipid raft connection between extrinsic and intrinsic apoptotic pathways