title: Molecular mechanisms of GD3-induced apoptosis in U-1242 MG glioma cells.
abstract: An increasing amount of evidence indicates that the disialoganglioside GD3 is involved in apoptosis in many cell lines. Our previous studies demonstrated that endogenous GD3 expression induced apoptosis in U-1242 MG glioma cells transfected with the GD3 synthase gene (U1242MG-GD3 cells). In this paper, we present further investigations on the molecular mechanisms of GD3-induced apoptosis in this cell line. We found that endogenously synthesized GD3 localizes to the caveolae of this cell line, where it promotes the localization of death receptor 5 (DR5), tumor necrosis factor receptor-1 (TNF-R1), and Fas (Apo-1) to the caveolae. In addition, caspase-8 was translocated to the caveolar fraction and cleaved; the cleaved proteins were then re-located into the high density fractions. However, GD3 had no effect on the distribution of the adapter protein Fas-associated death domain (FADD). We conclude that GD3 functions as a regulatory molecule early in the extrinsic apoptosis pathway.
authors.affiliation: Department of Pathology, The Ohio State University, 4170 Graves Hall, 333 W 10Th Ave, Columbus, OH 43210, USA.
authors.forename: O M
authors.initials: OM
authors.lastname: Omran
authors.forename: H E
authors.initials: HE
authors.lastname: Saqr
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Yates
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D005732:Gangliosides / Q000502:physiology*; D005910:Glioma / Q000473:pathology*; D006801:Humans
chemical_list: D005732:Gangliosides; C026226:ganglioside, GD3; D053181:Caspase 8