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Divalent cation tolerance protein binds to β-secretase and inhibits the processing of amyloid precursor protein☆

The deposition of amyloid-beta is a pathological hallmark of Alzheimer's disease. Amyloid-beta is derived from amyloid precursor protein through sequential proteolytic cleavages by β-secretase (beta-site amyloid precursor protein-cleaving enzyme 1) and γ-secretase. To further elucidate the role...

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Autores principales: Liu, Runzhong, Hou, Haibo, Yi, Xuelian, Wu, Shanwen, Zeng, Huan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145881/
https://www.ncbi.nlm.nih.gov/pubmed/25206392
http://dx.doi.org/10.3969/j.issn.1673-5374.2013.11.004
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author Liu, Runzhong
Hou, Haibo
Yi, Xuelian
Wu, Shanwen
Zeng, Huan
author_facet Liu, Runzhong
Hou, Haibo
Yi, Xuelian
Wu, Shanwen
Zeng, Huan
author_sort Liu, Runzhong
collection PubMed
description The deposition of amyloid-beta is a pathological hallmark of Alzheimer's disease. Amyloid-beta is derived from amyloid precursor protein through sequential proteolytic cleavages by β-secretase (beta-site amyloid precursor protein-cleaving enzyme 1) and γ-secretase. To further elucidate the roles of beta-site amyloid precursor protein-cleaving enzyme 1 in the development of Alzheimer's disease, a yeast two-hybrid system was used to screen a human embryonic brain cDNA library for proteins directly interacting with the intracellular domain of beta-site amyloid precursor protein-cleaving enzyme 1. A potential beta-site amyloid precursor protein-cleaving enzyme 1-interacting protein identified from the positive clones was divalent cation tolerance protein. Immunoprecipitation studies in the neuroblastoma cell line N2a showed that exogenous divalent cation tolerance protein interacts with endogenous beta-site amyloid precursor protein-cleaving enzyme 1. The overexpression of divalent cation tolerance protein did not affect beta-site amyloid precursor protein-cleaving enzyme 1 protein levels, but led to increased amyloid precursor protein levels in N2a/APP695 cells, with a concomitant reduction in the processing product amyloid precursor protein C-terminal fragment, indicating that divalent cation tolerance protein inhibits the processing of amyloid precursor protein. Our experimental findings suggest that divalent cation tolerance protein negatively regulates the function of beta-site amyloid precursor protein-cleaving enzyme 1. Thus, divalent cation tolerance protein could play a protective role in Alzheimer's disease.
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spelling pubmed-41458812014-09-09 Divalent cation tolerance protein binds to β-secretase and inhibits the processing of amyloid precursor protein☆ Liu, Runzhong Hou, Haibo Yi, Xuelian Wu, Shanwen Zeng, Huan Neural Regen Res Neurodegenerative Disease and Neural Regeneration The deposition of amyloid-beta is a pathological hallmark of Alzheimer's disease. Amyloid-beta is derived from amyloid precursor protein through sequential proteolytic cleavages by β-secretase (beta-site amyloid precursor protein-cleaving enzyme 1) and γ-secretase. To further elucidate the roles of beta-site amyloid precursor protein-cleaving enzyme 1 in the development of Alzheimer's disease, a yeast two-hybrid system was used to screen a human embryonic brain cDNA library for proteins directly interacting with the intracellular domain of beta-site amyloid precursor protein-cleaving enzyme 1. A potential beta-site amyloid precursor protein-cleaving enzyme 1-interacting protein identified from the positive clones was divalent cation tolerance protein. Immunoprecipitation studies in the neuroblastoma cell line N2a showed that exogenous divalent cation tolerance protein interacts with endogenous beta-site amyloid precursor protein-cleaving enzyme 1. The overexpression of divalent cation tolerance protein did not affect beta-site amyloid precursor protein-cleaving enzyme 1 protein levels, but led to increased amyloid precursor protein levels in N2a/APP695 cells, with a concomitant reduction in the processing product amyloid precursor protein C-terminal fragment, indicating that divalent cation tolerance protein inhibits the processing of amyloid precursor protein. Our experimental findings suggest that divalent cation tolerance protein negatively regulates the function of beta-site amyloid precursor protein-cleaving enzyme 1. Thus, divalent cation tolerance protein could play a protective role in Alzheimer's disease. Medknow Publications & Media Pvt Ltd 2013-04-15 /pmc/articles/PMC4145881/ /pubmed/25206392 http://dx.doi.org/10.3969/j.issn.1673-5374.2013.11.004 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Neurodegenerative Disease and Neural Regeneration
Liu, Runzhong
Hou, Haibo
Yi, Xuelian
Wu, Shanwen
Zeng, Huan
Divalent cation tolerance protein binds to β-secretase and inhibits the processing of amyloid precursor protein☆
title Divalent cation tolerance protein binds to β-secretase and inhibits the processing of amyloid precursor protein☆
title_full Divalent cation tolerance protein binds to β-secretase and inhibits the processing of amyloid precursor protein☆
title_fullStr Divalent cation tolerance protein binds to β-secretase and inhibits the processing of amyloid precursor protein☆
title_full_unstemmed Divalent cation tolerance protein binds to β-secretase and inhibits the processing of amyloid precursor protein☆
title_short Divalent cation tolerance protein binds to β-secretase and inhibits the processing of amyloid precursor protein☆
title_sort divalent cation tolerance protein binds to β-secretase and inhibits the processing of amyloid precursor protein☆
topic Neurodegenerative Disease and Neural Regeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145881/
https://www.ncbi.nlm.nih.gov/pubmed/25206392
http://dx.doi.org/10.3969/j.issn.1673-5374.2013.11.004
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