Characterization of the 5'-end region and the first two exons of the beta-protein precursor gene.
Human genomic clones encoding the promoter region and the first two exons of the beta-amyloid protein precursor (beta-APP) gene were isolated. The first exon is 205 base pairs (bp) long and encodes 19 amino acids. The second exon is 168 bp long and encodes 56 amino acids. The 5'-flanking sequence of the beta-APP gene was found to display promoter activity in several cell lines including PC12 cells where the highest activity was detected. The promoter region of this gene lacks the typical "TATAA" and "CAAT" boxes usually associated with eukaryotic promoters. Five copies of the GGGCGC sequence are located between positions -107 and -188 and one copy is located within the first exon of the beta-APP gene. Consensus sequences recognized by the transcription factors Sp1 and AP-1 are located upstream from the RNA start site. Palindromic sequences capable of forming stable hairpin-like structures are found around the main transcription initiation site. The structural characteristics of the beta-APP promoter indicate that multiple elements participate in the regulation of the expression of this gene.
La Fauci
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G
Mount Sinai School of Medicine, Department of Psychiatry, New York, NY 10029.
Lahiri
D K
DK
Salton
S R
SR
Robakis
N K
NK
D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D004720:Endonucleases; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D015345:Oligonucleotide Probes; D011498:Protein Precursors; D014157:Transcription Factors; D004247:DNA; D004720:Endonucleases; D004262:DNA Restriction Enzymes; D015719:Single-Strand Specific DNA and RNA Endonucleases