The Journal of Experimental Medicine
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Published 16 December 2002. doi:10.1084/jem.20020960
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© Rockefeller University Press, 0022-1007/2002/12/1535/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 12, December 16, 2002 1535-1541
Acetylation Suppresses the Proapoptotic Activity of GD3 Ganglioside

Florence Malisan1, Luigi Franchi1, Barbara Tomassini1, Natascia Ventura1, Ivano Condò1, Maria Rita Rippo1, Alessandra Rufini1, Laura Liberati1, Claudia Nachtigall2, Bernhard Kniep2 and Roberto Testi1

1 Laboratory of Immunology and Signal Transduction, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
2 Institute of Immunology, Technical University of Dresden, 01307 Dresden, Germany

Address correspondence to Roberto Testi, Laboratory of Immunology and Signal Transduction, Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata," via Montpellier 1, 00133 Rome, Italy. Phone: 39-06-7259-6503; Fax: 39-06-7259-6505; E-mail: tesrob{at}flashnet.it

GD3 synthase is rapidly activated in different cell types after specific apoptotic stimuli. De novo synthesized GD3 accumulates and contributes to the apoptotic program by relocating to mitochondrial membranes and inducing the release of apoptogenic factors. We found that sialic acid acetylation suppresses the proapoptotic activity of GD3. In fact, unlike GD3, 9-O-acetyl-GD3 is completely ineffective in inducing cytochrome c release and caspase-9 activation on isolated mitochondria and fails to induce the collapse of mitochondrial transmembrane potential and cellular apoptosis. Moreover, cells which are resistant to the overexpression of the GD3 synthase, actively convert de novo synthesized GD3 to 9-O-acetyl-GD3. The coexpression of GD3 synthase with a viral 9-O-acetyl esterase, which prevents 9-O-acetyl-GD3 accumulation, reconstitutes GD3 responsiveness and apoptosis. Finally, the expression of the 9-O-acetyl esterase is sufficient to induce apoptosis of glioblastomas which express high levels of 9-O-acetyl-GD3. Thus, sialic acid acetylation critically controls the proapoptotic activity of GD3.

Key Words: sialic acid • 9-O-acetyl GD3 • mitochondria • apoptosis • glioblastoma


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