Interleukin-1 stimulates the beta-amyloid precursor protein promoter.
1. Amyloid plaques found in the brains of Alzheimer's diseased patients are composed of the 42 amino acid beta-amyloid peptide (BAP) which is processed out of the larger amyloid precursor protein (APP). 2. To study the regulation of the APP gene expression, we have isolated the promoter region of this angle of this single-copy gene and produced a reporter gene system to determine if the promoter is responsive to agents that may cause the overproduction of APP leading to the abnormal accumulation of plaques in AD. 3. The promoter contains sequences homologous to heat shock elements, AP-1 binding sites, and phorbol ester-inducible sequences as well as GG-rich regions found in other constitutively expressed genes. 4. We show here that this promoter is inducible in cultured cells by interleukin-1 (IL-1) in a transient assay system and that the HSE and AP-1 binding site are required for this inducibility. 5. This induction of transcription from the APP promoter implies that this gene is responsive to tropic and/or trophic agents which may be present in the diseased brain.
Donnelly
R J
RJ
Millhauser Laboratories, Department of Psychiatry, NYU Medical Center, New York 10016.
Friedhoff
A J
AJ
Beer
B
B
Blume
A J
AJ
Vitek
M P
MP
D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21; D005813:Genes, Synthetic / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011498:Protein Precursors / Q000187:drug effects* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D011498:Protein Precursors; D011994:Recombinant Proteins