REQUIREMENT OF THE FAMILIAL ALZHEIMERS-DISEASE GENE PS2 FOR APOPTOSIS- OPPOSING EFFECT OF ALG-3

ALG-3, a truncated mouse homologue of the chromosome I familial Alzhei mer's disease gene PS2, rescues T hybridoma 3DO cells from T-cell rece ptor-induced apoptosis by inhibiting Fas ligand induction and Fas sign aling, Here we show that ALG-3 transfected 3DO cells express a COOH-te rminal PS2 polypeptide, Overexpression of PS2 in ALG-3 transfected 3DO cells reconstitutes sensitivity to receptor-induced cell death, sugge sting that the artificial PS2 polypeptide functions as a dominant nega tive mutant of PS2, ALG-3 and antisense PS2 protect PC12 cells from gl utamate-induced apoptosis but not from death induced by hydrogen perox ide or the free radical MPP(+). Thus, the PS2 gene is required for som e forms of cell death in diverse cell types, and its function is oppos ed by ALG-3.