Overexpression of a C-terminal fragment of presenilin 1 delays anti-Fas induced apoptosis in Jurkat cells.
Most cases of early onset familial Alzheimer's disease (FAD) involve mutations in presenilins (PS1 and PS2) genes. The C-terminal portion of PS2 is a homologue with an apoptosis-linked gene (ALG-3). To characterise the role of PS1 in apoptosis, we overexpressed the corresponding C-terminal fragment of PS1 (PS1-f) under the control of the tetracycline-responsive transactivator in Jurkat cells. The tight regulation of the expression of the 11 kDa PS1-f peptide was verified. A 50% inhibition of anti-Fas induced apoptosis was observed upon PS1-f transient overexpression compared to the repressed state. Stable transfectants selectively overexpressing PS1-f revealed a transient protective effect of 30% after apoptosis induction.
Vézina
J
J
Preclinical Research, Novartis Pharma Ltd., Basel, Switzerland. kurt.mueller@pharma.novartis.com
Tschopp
C
C
Andersen
E
E
Müller
K
K
D000544:Alzheimer Disease / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins; D006801:Humans; D019169:Jurkat Cells; D008164:Luminescent Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D053764:Presenilin-1; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013752:Tetracycline / Q000494:pharmacology; D014162:Transfection; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D008164:Luminescent Proteins; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D049452:Green Fluorescent Proteins; D013752:Tetracycline