Requirement of the Familial Alzheimer's Disease Gene PS2 for Apoptosis
OPPOSING EFFECT OF ALG-3*
- Pasquale Vito†,
- Benjamin Wolozin§¶,
- J. Kelly Ganjei†,
- Katsunori Iwasaki§,
- Emanuela Lacanᆠand
- Luciano D'Adamio†∥
- From the † T-Cell Molecular Biology Unit, Laboratory of Cellular and Molecular Immunology, NIAID, National Institutes of Health, and the
- §Unit on Alzheimer Biology, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892
- ∥ To whom correspondence should be addressed: T-cell Molecular Biology Unit, Laboratory of Cellular and Molecular Immunology, NIAID, NIH, Bldg. 4, Rm. 111, Bethesda, MD 20892. Tel.: 301-496-3842; Fax: 301-402-3184; E-mail: ldadamio{at}atlas.niaid.nih.gov.
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.
Footnotes
-
↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) U49111[GenBank] (ALG-3) and U57324[GenBank] (mouse PS2).
-
↵1 The abbreviation used are:
- PCD
-
programmed cell death
- TCR
-
T-cell receptor
- AD
-
Alzheimer's disease
- PAGE
-
polyacrylamide gel electrophoresis
- β-Gal
-
β-galactosidase
- CMV
-
cytomegalovirus
- PBS
-
phosphate-buffered saline
- MTT
-
3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide.
-
- Received July 23, 1996.
- Revision received October 3, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
