title: Requirement of the familial Alzheimer's disease gene PS2 for apoptosis. Opposing effect of ALG-3.
abstract: ALG-3, a truncated mouse homologue of the chromosome 1 familial Alzheimer's disease gene PS2, rescues T hybridoma 3DO cells from T-cell receptor-induced apoptosis by inhibiting Fas ligand induction and Fas signaling. Here we show that ALG-3 transfected 3DO cells express a COOH-terminal PS2 polypeptide. Overexpression of PS2 in ALG-3 transfected 3DO cells reconstitutes sensitivity to receptor-induced cell death, suggesting that the artificial PS2 polypeptide functions as a dominant negative mutant of PS2. ALG-3 and antisense PS2 protect PC12 cells from glutamate-induced apoptosis but not from death induced by hydrogen peroxide or the free radical MPP+. Thus, the PS2 gene is required for some forms of cell death in diverse cell types, and its function is opposed by ALG-3.
authors.affiliation: T-Cell Molecular Biology Unit, Laboratory of Cellular and Molecular Immunology, NIAID, National Institutes of Health, Maryland 20892, USA. ldadamio@atlas.niaid.nih.gov
authors.forename: P
authors.initials: P
authors.lastname: Vito
authors.forename: B
authors.initials: B
authors.lastname: Wolozin
authors.forename: J K
authors.initials: JK
authors.lastname: Ganjei
authors.forename: K
authors.initials: K
authors.lastname: Iwasaki
authors.forename: E
authors.initials: E
authors.lastname: Lacanà
authors.forename: L
authors.initials: L
authors.lastname: D'Adamio
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D053766:Presenilin-2; D016415:Sequence Alignment; D014162:Transfection
chemical_list: D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; C095101:Psen2 protein, mouse