Gene structure and organization of the human β‐secretase ( BACE ) promoter
| العنوان: | Gene structure and organization of the human β‐secretase ( BACE ) promoter |
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| المؤلفون: | Yuan Wen Ge, Debomoy K. Lahiri, Rachel Kinsey, Bryan Maloney, Kumar Sambamurti |
| المصدر: | The FASEB Journal. 18:1034-1036 |
| بيانات النشر: | Wiley, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Untranslated region, 5' Flanking Region, Molecular Sequence Data, Restriction Mapping, Response Elements, CREB, Biochemistry, Mice, Alzheimer Disease, Transcription (biology), Consensus Sequence, Endopeptidases, Genetics, Animals, Aspartic Acid Endopeptidases, Humans, Cloning, Molecular, Promoter Regions, Genetic, Molecular Biology, Gene, Transcription factor, Base Composition, Binding Sites, Base Sequence, biology, Chemistry, Chromosomes, Human, Pair 11, Promoter, Exons, Genomics, Introns, Rats, Cell biology, DNA binding site, biology.protein, Amyloid Precursor Protein Secretases, Transcription Initiation Site, 5' Untranslated Regions, Amyloid precursor protein secretase, Transcription Factors, Biotechnology |
| الوصف: | The first step in the generation of the amyloid-beta peptide (Abeta) deposited in the brains of patients with Alzheimer's disease (AD) is the processing of the larger Abeta precursor protein (APP) by an integral membrane aspartyl protease named the beta-site APP-cleaving enzyme (BACE). We present the genomic organization of the BACE gene. BACE mRNAs are synthesized as nine exons and eight introns from a 30.6 kb region of chromosome 11q23.2-11q23.3. Regulation of BACE may play an important role in regulating the levels of Abeta produced and is therefore likely to play an important role in AD. Herein, we report the cloning and detailed analysis of 3765 nucleotides of the promoter region of BACE and 364 nucleotides of the 5' untranslated region of the BACE mRNA (5' UTR). Characteristic "CAAT" and "TATA" boxes are absent within 1.5 kb of the transcription start site (TSS). The promoter region and 5' UTR contain multiple transcription factor binding sites, such as activator protein (AP)1, AP2, cAMP response element binding protein (CREB), estrogen responsive element (ERE), glucocorticoid responsive element (GRE), "GC" box, nuclear factor (NF)-kappaB, signal transducer and activator of transcription (STAT)1, stimulating protein (SP)1, metal-regulatory elements, and possible Zeste binding sites. Limited interspecies similarity was observed between the human sequence and corresponding genomic DNA from the rat and mouse sequences, but several transcription factor-binding sites are conserved. Thus, the BACE gene contains basal regulatory elements, inducible features and sites for regulated activity by various transcription factors. These results identify the important regions for functional analysis of the binding domains and neuron-specific expression (1). Such a study will allow us to further examine the possible role of changes in the promoter of BACE in AD pathogenesis. |
| تدمد: | 1530-6860 0892-6638 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bace005873ffb8f4c2b907b65a0143e5Test https://doi.org/10.1096/fj.03-1378fjeTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....bace005873ffb8f4c2b907b65a0143e5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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