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Science 12 September 1997:
Vol. 277. no. 5332, pp. 1652 - 1655
DOI: 10.1126/science.277.5332.1652
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Reports

Requirement for GD3 Ganglioside in CD95- and Ceramide-Induced Apoptosis

Ruggero De Maria, Luisa Lenti, Florence Malisan, Federica d'Agostino, Barbara Tomassini, Ann Zeuner, Maria Rita Rippo, Roberto Testi *

Gangliosides participate in development and tissue differentiation. Cross-linking of the apoptosis-inducing CD95 protein (also called Fas or APO-1) in lymphoid and myeloid tumor cells triggered GD3 ganglioside synthesis and transient accumulation. CD95-induced GD3 accumulation depended on integral receptor "death domains" and on activation of a family of cysteine proteases called caspases. Cell-permeating ceramides, which are potent inducers of apoptosis, also triggered GD3 synthesis. GD3 disrupted mitochondrial transmembrane potential (Delta Psi m), and induced apoptosis, in a caspase-independent fashion. Transient overexpression of the GD3 synthase gene directly triggered apoptosis. Pharmacological inhibition of GD3 synthesis and exposure to GD3 synthase antisense oligodeoxynucleotides prevented CD95-induced apoptosis. Thus, GD3 ganglioside mediates the propagation of CD95-generated apoptotic signals in hematopoietic cells.

R. De Maria, F. Malisan, B. Tomassini, A. Zeuner, M. R. Rippo, R. Testi, Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata," 00133 Rome, Italy.
L. Lenti and F. d'Agostino, Department of Experimental Medicine and Pathology, University of Rome "La Sapienza," 00161 Rome, Italy.
*   To whom correspondence should be addressed. E-mail: tesrob{at}flashnet.it

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J. Biol. Chem. 276, 44504-44511
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Science. ISSN 0036-8075 (print), 1095-9203 (online)