Glycosphingolipids are essential components of plasma membrane and act as antigens, mediators of cell adhesion, and modulators of signal transduction. Following activation of the Fas receptor, gangliosides are recuited in various intracellular compartments. We have evaluated whether the pro-apoptotic anti-CD95 antibody induces a nuclear localization of GD3 in HUT-78 cells. Our data shows that GD3 translocation from cytosol to nuclei is strongly correlated to concomitant rapid phosphorylation of histone HI shortly after induction of apoptosis. This work advances the hypothesis that GD3 induces a post-translational modification of historic HI thus influencing the apoptosis process through transcriptional activation/repression of specific genes. (c) 2008 Elsevier Inc. All rights reserved.