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Regulation of amyloid precursor protein processing by its KFERQ motif
Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer’s disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consen...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Biochemistry and Molecular Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070722/ https://www.ncbi.nlm.nih.gov/pubmed/26779997 http://dx.doi.org/10.5483/BMBRep.2016.49.6.212 |
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author | Park, Ji-Seon Kim, Dong-Hou Yoon, Seung-Yong |
author_facet | Park, Ji-Seon Kim, Dong-Hou Yoon, Seung-Yong |
author_sort | Park, Ji-Seon |
collection | PubMed |
description | Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer’s disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy. [BMB Reports 2016;49(6): 337-342] |
format | Online Article Text |
id | pubmed-5070722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Korean Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-50707222016-10-20 Regulation of amyloid precursor protein processing by its KFERQ motif Park, Ji-Seon Kim, Dong-Hou Yoon, Seung-Yong BMB Rep Research Articles Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer’s disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy. [BMB Reports 2016;49(6): 337-342] Korean Society for Biochemistry and Molecular Biology 2016-06-30 /pmc/articles/PMC5070722/ /pubmed/26779997 http://dx.doi.org/10.5483/BMBRep.2016.49.6.212 Text en Copyright © 2016, Korean Society for Biochemistry and Molecular Biology http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Park, Ji-Seon Kim, Dong-Hou Yoon, Seung-Yong Regulation of amyloid precursor protein processing by its KFERQ motif |
title | Regulation of amyloid precursor protein processing by its KFERQ motif |
title_full | Regulation of amyloid precursor protein processing by its KFERQ motif |
title_fullStr | Regulation of amyloid precursor protein processing by its KFERQ motif |
title_full_unstemmed | Regulation of amyloid precursor protein processing by its KFERQ motif |
title_short | Regulation of amyloid precursor protein processing by its KFERQ motif |
title_sort | regulation of amyloid precursor protein processing by its kferq motif |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070722/ https://www.ncbi.nlm.nih.gov/pubmed/26779997 http://dx.doi.org/10.5483/BMBRep.2016.49.6.212 |
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