ArticlePloS one2013
Turnover of amyloid precursor protein family members determines their nuclear signaling capability.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Amyloid precursor-like protein 2 expression in macrophages: differentiation and M1/M2 macrophage dynamics.Frontiers in oncology · 2025Article
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- The amyloid precursor protein intracellular domain induces sleep disruptions and its nuclear localization fluctuates in circadian pacemaker neurons in Drosophila and mice.Neurobiology of disease · 2024Article
- Physiopathological mechanisms underlying Alzheimer's disease: a narrative review.Dementia & neuropsychologia · 2024Review
- A delta-secretase-truncated APP fragment activates CEBPB, mediating Alzheimer's disease pathologies.Brain : a journal of neurology · 2021Article
- FoxA2 and RNA Pol II mediate human islet amyloid polypeptide turnover in ER-stressed pancreatic β-cells.The Biochemical journal · 2021Article
- The cellular expression and proteolytic processing of the amyloid precursor protein is independent of TDP-43.Bioscience reports · 2020Article
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
- Click Chemistry-mediated Biotinylation Reveals a Function for the Protease BACE1 in Modulating the Neuronal Surface Glycoproteome.Molecular & cellular proteomics : MCP · 2018Article
- APLP1 is endoproteolytically cleaved by γ-secretase without previous ectodomain shedding.Scientific reports · 2018Article
- APLP1 Is a Synaptic Cell Adhesion Molecule, Supporting Maintenance of Dendritic Spines and Basal Synaptic Transmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Modulation of BAG3 Expression and Proteasomal Activity by sAPPα Does Not Require Membrane-Tethered Holo-APP.Molecular neurobiology · 2016Article
- APP Receptor? To Be or Not To Be.Trends in pharmacological sciences · 2016Review
- Article
- Amyloid Precursor Protein (APP) Metabolites APP Intracellular Fragment (AICD), Aβ42, and Tau in Nuclear Roles.The Journal of biological chemistry · 2015Review
- APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation.Cell death & disease · 2015Article
- A synthetic antibody fragment targeting nicastrin affects assembly and trafficking of γ-secretase.The Journal of biological chemistry · 2014Article
- Nuclear translocation uncovers the amyloid peptide Aβ42 as a regulator of gene transcription.The Journal of biological chemistry · 2014Article
- Biochemical assessment of precuneus and posterior cingulate gyrus in the context of brain aging and Alzheimer's disease.PloS one · 2014Article
- Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer's Disease.Frontiers in aging neuroscience · 2013Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid precursor protein (APP) as well as its homologues, APP-like protein 1 and 2 (APLP1 and APLP2), are cleaved by α-, β-, and γ-secretases, resulting in the release of their intracellular domains (ICDs). We have shown that the APP intracellular domain (AICD) is transported to the nucleus by Fe65 where they jointly bind the histone acetyltransferase Tip60 and localize to spherical nuclear complexes (AFT complexes), which are thought to be sites of transcription. We have now analyzed the subcellular localization and turnover of the APP family members. Similarly to AICD, the ICD of APLP2 localizes to spherical nuclear complexes together with Fe65 and Tip60. In contrast, the ICD of APLP1, despite binding to Fe65, does not translocate to the nucleus. In addition, APLP1 predominantly localizes to the plasma membrane, whereas APP and APLP2 are detected in vesicular structures. APLP1 also demonstrates a much slower turnover of the full-length protein compared to APP and APLP2. We further show that the ICDs of all APP family members are degraded by the proteasome and that the N-terminal amino acids of ICDs determine ICD degradation rate. Together, our results suggest that different nuclear signaling capabilities of APP family members are due to different rates of full-length protein processing and ICD proteasomal degradation. Our results provide evidence in support of a common nuclear signaling function for APP and APLP2 that is absent in APLP1, but suggest that APLP1 has a regulatory role in the nuclear translocation of APP family ICDs due to the sequestration of Fe65.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.