ArticleMolecular and cellular biology2006
Leaky scanning and reinitiation regulate BACE1 gene expression.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Regulation of translation by upstream translation initiation codons of surfactant protein A1 splice variants.American journal of physiology. Lung cellular and molecular physiology · 2015Trial
- ARL6IP1 mediates small-molecule-induced alleviation of Alzheimer pathology through FXR1-dependent BACE1 translation initiation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Functional Meaning of 5'UTR in Protein-Coding Genes.International journal of molecular sciences · 2023Review
- Sex-Specific Regulation of β-Secretase: A Novel Estrogen Response Element (ERE)-Dependent Mechanism in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Translational Inhibition of α-Neurexin 2.Scientific reports · 2020Article
- Amyloid Beta-Peptide Increases BACE1 Translation through the Phosphorylation of the Eukaryotic Initiation Factor-2Oxidative medicine and cellular longevity · 2020Article
- Article
- BACE1 Translation: At the Crossroads Between Alzheimer's Disease Neurodegeneration and Memory Consolidation.Journal of Alzheimer's disease reports · 2019Review
- Fructosuria and recurrent hypoglycemia in a patient with a novel c.1693T>A variant in the 3' untranslated region of the aldolase B gene.SAGE open medical case reports · 2019Article
- Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments.The EMBO journal · 2018Review
- Hijacking of the AP-1 Signaling Pathway during Development of ATL.Frontiers in microbiology · 2017Review
- Two novel DNA motifs are essential for BACE1 gene transcription.Scientific reports · 2014Article
- Down-regulation of MIF by NFκB under hypoxia accelerated neuronal loss during stroke.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- MicroRNA-339-5p down-regulates protein expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer disease subjects.The Journal of biological chemistry · 2014Article
- uORFdb--a comprehensive literature database on eukaryotic uORF biology.Nucleic acids research · 2014Article
- A novel mutation in the upstream open reading frame of the CDKN1B gene causes a MEN4 phenotype.PLoS genetics · 2013Article
- Inhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes.The Journal of clinical investigation · 2013Article
- Gene expression regulation by upstream open reading frames and human disease.PLoS genetics · 2013Review
- Depletion of GGA1 and GGA3 mediates postinjury elevation of BACE1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- The Membrane-Bound Aspartyl Protease BACE1: Molecular and Functional Properties in Alzheimer's Disease and Beyond.Frontiers in physiology · 2012Article
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Authors and funding
2 authors.
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No grant is acknowledged in the PubMed record.
Abstract
beta-Site beta-amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is the beta-secretase in vivo for processing APP to generate amyloid beta protein (Abeta). Abeta deposition in the brain is the hallmark of Alzheimer's disease (AD) neuropathology. Inhibition of BACE1 activity has major pharmaceutical potential for AD treatment. The expression of the BACE1 gene is relatively low in vivo. The control of BACE1 expression has not been well defined. There are six upstream AUGs (uAUGs) in the 5' leader sequence of the human BACE1 mRNA. We investigated the role of the promoter and the uATGs in the 5' untranslated region (UTR) of the human BACE1 gene in BACE1 gene transcription and translation initiation. Our results show that the first and second uATGs are the integral part of the core minimal promoter of the human BACE1 gene, while the third uAUG is skipped over by ribosomal scanning. The fourth uAUG can function as a translation initiation codon, and deletion or mutation of this uAUG increases downstream gene expression. The fourth uAUG of the BACE1 5'UTR is responsible for inhibiting the expression of BACE1. Translation initiation by the BACE1 uAUGs and physiological AUG requires intact eIF4G. Our results demonstrate that during human BACE1 gene expression, ribosomes skipped some uAUGs by leaky scanning and translated an upstream open reading frame, initiated efficiently at the fourth uAUG, and subsequently reinitiated BACE1 translation at the physiological AUG site. Such leaky scanning and reinitiation resulted in weak expression of BACE1 under normal conditions. Alterations of the leaky scanning and reinitiation in BACE1 gene expression could play an important role in AD pathogenesis.
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