ArticleThe Journal of biological chemistry2010
Expression of the anti-amyloidogenic secretase ADAM10 is suppressed by its 5'-untranslated region.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- Altered expression and mutations in cell cycle genes CCND1, CDK4, CDKN2B and TP53 are associated with Pakistani breast cancer patients.Molecular biology reports · 2026Article
- Glycogen synthase kinase 3 (GSK3) inhibition: a potential therapeutic strategy for Alzheimer's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- A Valuable Target for Therapy: The Metalloproteinase ADAM10.Current protein & peptide science · 2025Review
- SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The Functional Meaning of 5'UTR in Protein-Coding Genes.International journal of molecular sciences · 2023Review
- Sulfuretin exerts diversified functions in the processing of amyloid precursor protein.Genes & diseases · 2021Article
- GDE2-RECK controls ADAM10 α-secretase-mediated cleavage of amyloid precursor protein.Science translational medicine · 2021Article
- Neuroprotective Properties of Resveratrol and Its Derivatives-Influence on Potential Mechanisms Leading to the Development of Alzheimer's Disease.International journal of molecular sciences · 2020Article
- Dendritic Spines in Alzheimer's Disease: How the Actin Cytoskeleton Contributes to Synaptic Failure.International journal of molecular sciences · 2020Review
- Stage-dependent involvement of ADAM10 and its significance in epileptic seizures.Journal of cellular and molecular medicine · 2019Review
- Naphthalene Diimides as Multimodal G-Quadruplex-Selective Ligands.Molecules (Basel, Switzerland) · 2019Review
- Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Cosmosiin Increases ADAM10 Expression via Mechanisms Involving 5'UTR and PI3K Signaling.Frontiers in molecular neuroscience · 2018Article
- Regulation of Alpha-Secretase ADAM10Frontiers in molecular neuroscience · 2017Review
- C6 Glioma-Secreted NGF and FGF2 Regulate Neuronal APP Processing Through Up-Regulation of ADAM10 and Down-Regulation of BACE1, Respectively.Journal of molecular neuroscience : MN · 2016Article
- Progranulin transcripts with short and long 5' untranslated regions (UTRs) are differentially expressed via posttranscriptional and translational repression.The Journal of biological chemistry · 2014Article
- MicroRNA-144 is regulated by activator protein-1 (AP-1) and decreases expression of Alzheimer disease-related a disintegrin and metalloprotease 10 (ADAM10).The Journal of biological chemistry · 2013Article
- ADAM10 expression and promoter haplotype in Alzheimer's disease.Neurobiology of aging · 2012Article
- Regulation of α-secretase ADAM10 expression and activity.Experimental brain research · 2012Review
- Activation of NMDA receptors upregulates a disintegrin and metalloproteinase 10 via a Wnt/MAPK signaling pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolytic processing of the amyloid precursor protein by alpha-secretase prevents formation of the amyloid beta-peptide (Abeta), which is the main constituent of amyloid plaques in brains of Alzheimer disease (AD) patients. alpha-Secretase activity is decreased in AD, and overexpression of the alpha-secretase ADAM10 (a disintegrin and metalloprotease 10) in an AD animal model prevents amyloid pathology. ADAM10 has a 444-nucleotide-long, very GC-rich 5'-untranslated region (5'-UTR) with two upstream open reading frames. Because similar properties of 5'-UTRs are found in transcripts of many genes, which are regulated by translational control mechanisms, we asked whether ADAM10 expression is translationally controlled by its 5'-UTR. We demonstrate that the 5'-UTR of ADAM10 represses the rate of ADAM10 translation. In the absence of the 5'-UTR, we observed a significant increase of ADAM10 protein levels in HEK293 cells, whereas mRNA levels were not changed. Moreover, the 5'-UTR of ADAM10 inhibits translation of a luciferase reporter in an in vitro transcription/translation assay. Successive deletion of the first half of the ADAM10 5'-UTR revealed a striking increase in ADAM10 protein expression in HEK293 cells, suggesting that this part of the 5'-UTR contains inhibitory elements for translation. Moreover, we detect an enhanced alpha-secretase activity and consequently reduced Abeta levels in the conditioned medium of HEK293 cells expressing both amyloid precursor protein and a 5'-UTR-ADAM10 deletion construct lacking the first half of the 5'-UTR. Thus, we provide evidence that the 5'-UTR of ADAM10 may have an important role for post-transcriptional regulation of ADAM10 expression and consequently Abeta production.
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