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The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast
Apoptosis is a form of programmed cell death which is essential for the growth of dividing human cells whereas, in contrast, it is deleterious for post-mitotic cells such as neurons. Bax and α-synuclein are two human proteins which play a role in the induction of neuronal apoptosis in neurodegenerat...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468099/ https://www.ncbi.nlm.nih.gov/pubmed/32794578 http://dx.doi.org/10.1042/BSR20201912 |
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author | Akintade, Damilare D. Chaudhuri, Bhabatosh |
author_facet | Akintade, Damilare D. Chaudhuri, Bhabatosh |
author_sort | Akintade, Damilare D. |
collection | PubMed |
description | Apoptosis is a form of programmed cell death which is essential for the growth of dividing human cells whereas, in contrast, it is deleterious for post-mitotic cells such as neurons. Bax and α-synuclein are two human proteins which play a role in the induction of neuronal apoptosis in neurodegenerative diseases like Alzheimer’s and Parkinson’s. Human Bax and α-synuclein also induce cell death when expressed in baker’s yeast, Saccharomyces cerevisiae. Quite unexpectedly, the human α-synuclein gene had been identified as an inhibitor of pro-apoptotic Bax using a yeast-based screen of a human hippocampal cDNA library. Plasmids were constructed with different promoters, which allow expression of wildtype and Parkinson’s disease (PD)-related mutant α-synuclein genes, from (i) multi-copy 2µ (episomal) plasmids and (ii) integrative plasmids that compel expression of genes from chromosomal sites in varying copy numbers (1–3). All α-synuclein-containing plasmids were introduced, through transformation, into a yeast strain which already contained a chromosomally integrated copy of Bax. It is for the first time that it was observed that, depending on gene dosage, only wildtype α-synuclein is anti-apoptotic while mutant α-synuclein is not. The results also indicate that wildtype α-synuclein has a remarkable ability to manifest two contrasting effects depending on its level of expression: (i) normally, it would negate apoptosis but (ii) when overexpressed, it tends to induce apoptosis which is probably what happens in PD. |
format | Online Article Text |
id | pubmed-7468099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74680992020-09-11 The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast Akintade, Damilare D. Chaudhuri, Bhabatosh Biosci Rep Cell Death & Injury Apoptosis is a form of programmed cell death which is essential for the growth of dividing human cells whereas, in contrast, it is deleterious for post-mitotic cells such as neurons. Bax and α-synuclein are two human proteins which play a role in the induction of neuronal apoptosis in neurodegenerative diseases like Alzheimer’s and Parkinson’s. Human Bax and α-synuclein also induce cell death when expressed in baker’s yeast, Saccharomyces cerevisiae. Quite unexpectedly, the human α-synuclein gene had been identified as an inhibitor of pro-apoptotic Bax using a yeast-based screen of a human hippocampal cDNA library. Plasmids were constructed with different promoters, which allow expression of wildtype and Parkinson’s disease (PD)-related mutant α-synuclein genes, from (i) multi-copy 2µ (episomal) plasmids and (ii) integrative plasmids that compel expression of genes from chromosomal sites in varying copy numbers (1–3). All α-synuclein-containing plasmids were introduced, through transformation, into a yeast strain which already contained a chromosomally integrated copy of Bax. It is for the first time that it was observed that, depending on gene dosage, only wildtype α-synuclein is anti-apoptotic while mutant α-synuclein is not. The results also indicate that wildtype α-synuclein has a remarkable ability to manifest two contrasting effects depending on its level of expression: (i) normally, it would negate apoptosis but (ii) when overexpressed, it tends to induce apoptosis which is probably what happens in PD. Portland Press Ltd. 2020-09-02 /pmc/articles/PMC7468099/ /pubmed/32794578 http://dx.doi.org/10.1042/BSR20201912 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). |
spellingShingle | Cell Death & Injury Akintade, Damilare D. Chaudhuri, Bhabatosh The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast |
title | The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast |
title_full | The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast |
title_fullStr | The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast |
title_full_unstemmed | The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast |
title_short | The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast |
title_sort | effect of copy number on α-synuclein’s toxicity and its protective role in bax-induced apoptosis, in yeast |
topic | Cell Death & Injury |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468099/ https://www.ncbi.nlm.nih.gov/pubmed/32794578 http://dx.doi.org/10.1042/BSR20201912 |
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