Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Mol Neurosci
2006 Jan 01;291:65-80. doi: 10.1385/JMN:29:1:65.
Show Gene links
Show Anatomy links
Functional domains of the BACE1 and BACE2 promoters and mechanisms of transcriptional suppression of the BACE2 promoter in normal neuronal cells.
Lahiri DK
,
Maloney B
,
Ge YW
.
???displayArticle.abstract???
The beta-amyloid (Abeta) protein present in the neuritic plaques of Alzheimer's disease is cleaved from Abeta precursor protein (APP) by beta- and gamma-secretases. Following identification of beta-APP cleaving enzyme (BACE1) as the beta-secretase, a homologous beta-secretase 2 (BACE2) was described. Our goal is to characterize the regulatory region of the BACE genes. We compare functional domains within the BACE1 and BACE2 regulatory regions. Both BACE genes lack canonical TATAand CAAT boxes, but they contain distinguishing transcription start sites and transcription factor-binding sites. The BACE1 sequence contains more repetitive elements than does BACE2 (no elements). Regulatory domains do not overlap strongly between the two promoter regions. The BACE1upstream sequence contains both negative and positive domains, separated from the transcription seat by a long neutral domain. The corresponding BACE2sequence consists of a weakly positive domain directly upstream of a strongly positive domain, near a functionally active domain. DNA-protein interaction was corroborated by functional data. In primary rat cortical cultures, BACE1-driven reporter protein's expression was twice that of BACE2- driven reporter. The BACE2 gene promoter relatively reduced function in neuronal cells compared with BACE1. The BACE1 gene might operate through a single transcriptional control site. BACE2 operates through dual transcriptional control sites. Two (or more) regulatory pathways might control transcription in BACE2. Thus, BACE2 is partially suppressed in normal neuronal cells and likely to be a highly regulated gene expressed in a particularly tissue-specific fashion.
Acquati,
The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region.
2000, Pubmed
Acquati,
The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region.
2000,
Pubmed
Basi,
Antagonistic effects of beta-site amyloid precursor protein-cleaving enzymes 1 and 2 on beta-amyloid peptide production in cells.
2003,
Pubmed
Bennett,
Expression analysis of BACE2 in brain and peripheral tissues.
2000,
Pubmed
Benson,
GenBank.
2005,
Pubmed
Bradford,
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
1976,
Pubmed
Cady,
Age-related differences in NMDA responses in cultured rat hippocampal neurons.
2001,
Pubmed
Carrodeguas,
The chick embryo appears as a natural model for research in beta-amyloid precursor protein processing.
2005,
Pubmed
Chen,
Human CD1D gene has TATA boxless dual promoters: an SP1-binding element determines the function of the proximal promoter.
2004,
Pubmed
Christensen,
Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta-secretase, by Sp1.
2004,
Pubmed
Corpet,
Multiple sequence alignment with hierarchical clustering.
1988,
Pubmed
Farzan,
BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.
2000,
Pubmed
Ge,
Functional characterization of the 5' flanking region of the BACE gene: identification of a 91 bp fragment involved in basal level of BACE promoter expression.
2004,
Pubmed
Ghosh,
Efficient DNA transfection in neuronal and astrocytic cell lines.
2000,
Pubmed
Girish,
Affordable image analysis using NIH Image/ImageJ.
2004,
Pubmed
Hardy,
The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics.
2002,
Pubmed
Hussain,
Identification of a novel aspartic protease (Asp 2) as beta-secretase.
1999,
Pubmed
Ikeo,
Evolutionary origin of a Kunitz-type trypsin inhibitor domain inserted in the amyloid beta precursor protein of Alzheimer's disease.
1992,
Pubmed
Jurka,
CENSOR--a program for identification and elimination of repetitive elements from DNA sequences.
1996,
Pubmed
Kim,
Neuron-restrictive silencer factor (NRSF) functions as a repressor in neuronal cells to regulate the mu opioid receptor gene.
2004,
Pubmed
Kitami,
The unique 5-flanking region of the human basic calponin gene.
1999,
Pubmed
Kitami,
Molecular structure and function of rat platelet-derived growth factor beta-receptor gene promoter.
1998,
Pubmed
Klein,
Genetic and genomic tools for Xenopus research: The NIH Xenopus initiative.
2002,
Pubmed
,
Xenbase
Kong,
A high-resolution recombination map of the human genome.
2002,
Pubmed
Lahiri,
Characterization of the APP proximal promoter and 5'-untranslated regions: identification of cell type-specific domains and implications in APP gene expression and Alzheimer's disease.
2005,
Pubmed
Lahiri,
BACE1 gene promoter is differentially regulated: detection of a novel promoter region for its cell type-specific regulation.
2006,
Pubmed
Lahiri,
Functional characterization of the 5'-regulatory region of the murine apolipoprotein gene.
2002,
Pubmed
Lahiri,
Electrophoretic mobility shift assay for the detection of specific DNA-protein complex in nuclear extracts from the cultured cells and frozen autopsy human brain tissue.
2000,
Pubmed
Lahiri,
Characterization of two APP gene promoter polymorphisms that appear to influence risk of late-onset Alzheimer's disease.
2005,
Pubmed
Lahiri,
Apolipoprotein gene and its interaction with the environmentally driven risk factors: molecular, genetic and epidemiological studies of Alzheimer's disease.
2004,
Pubmed
Lahiri,
A critical analysis of new molecular targets and strategies for drug developments in Alzheimer's disease.
2003,
Pubmed
Lahiri,
Promoter activity of the beta-amyloid precursor protein gene is negatively modulated by an upstream regulatory element.
1999,
Pubmed
Li,
Characterization of mouse cathepsin K gene, the gene promoter, and the gene expression.
1999,
Pubmed
Lin,
Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein.
2000,
Pubmed
Long,
The greatest step in vertebrate history: a paleobiological review of the fish-tetrapod transition.
2004,
Pubmed
Maloney,
Characterization of the human beta-secretase 2 (BACE2) 5'-flanking region: identification of a 268-bp region as the basal BACE2 promoter.
2006,
Pubmed
Maloney,
Presence of a "CAGA box" in the APP gene unique to amyloid plaque-forming species and absent in all APLP-1/2 genes: implications in Alzheimer's disease.
2004,
Pubmed
Neve,
Alzheimer's disease: dysfunction of a signalling pathway mediated by the amyloid precursor protein?
2001,
Pubmed
Pruitt,
NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins.
2005,
Pubmed
Sambamurti,
Gene structure and organization of the human beta-secretase (BACE) promoter.
2004,
Pubmed
Schoenherr,
The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes.
1995,
Pubmed
Solans,
A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase.
2000,
Pubmed
Song,
Molecular cloning of the promoter of the gene encoding the Rhesus monkey beta-amyloid precursor protein: structural characterization and a comparative study with other species.
1998,
Pubmed
Stamatoyannopoulos,
The genomics of gene expression.
2004,
Pubmed
Sun,
Distinct transcriptional regulation and function of the human BACE2 and BACE1 genes.
2005,
Pubmed
Vassar,
Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.
1999,
Pubmed
Waisman,
In vitro regulation of human hepatitis B virus core gene transcription.
1990,
Pubmed
Xie,
Two closely linked but separable promoters for human neuronal nitric oxide synthase gene transcription.
1995,
Pubmed
Yan,
Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity.
1999,
Pubmed
Yan,
BACE2 functions as an alternative alpha-secretase in cells.
2001,
Pubmed