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The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin
The Blm10/PA200 family of proteasome activators modulates the peptidase activity of the core particle (20S CP). They participate in opening the 20S CP gate, thus facilitating the degradation of unstructured proteins such as tau and Dnm1 in a ubiquitin- and ATP-independent manner. Furthermore, PA200...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699873/ https://www.ncbi.nlm.nih.gov/pubmed/33233776 http://dx.doi.org/10.3390/biom10111581 |
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author | Aladdin, Azzam Yao, Yanhua Yang, Ciyu Kahlert, Günther Ghani, Marvi Király, Nikolett Boratkó, Anita Uray, Karen Dittmar, Gunnar Tar, Krisztina |
author_facet | Aladdin, Azzam Yao, Yanhua Yang, Ciyu Kahlert, Günther Ghani, Marvi Király, Nikolett Boratkó, Anita Uray, Karen Dittmar, Gunnar Tar, Krisztina |
author_sort | Aladdin, Azzam |
collection | PubMed |
description | The Blm10/PA200 family of proteasome activators modulates the peptidase activity of the core particle (20S CP). They participate in opening the 20S CP gate, thus facilitating the degradation of unstructured proteins such as tau and Dnm1 in a ubiquitin- and ATP-independent manner. Furthermore, PA200 also participates in the degradation of acetylated histones. In our study, we use a combination of yeast and human cell systems to investigate the role of Blm10/PA200 in the degradation of N-terminal Huntingtin fragments (N-Htt). We demonstrate that the human PA200 binds to N-Htt. The loss of Blm10 in yeast or PA200 in human cells results in increased mutant N-Htt aggregate formation and elevated cellular toxicity. Furthermore, Blm10 in vitro accelerates the proteasomal degradation of soluble N-Htt. Collectively, our data suggest N-Htt as a new substrate for Blm10/PA200-proteasomes and point to new approaches in Huntington’s disease (HD) research. |
format | Online Article Text |
id | pubmed-7699873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76998732020-11-29 The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin Aladdin, Azzam Yao, Yanhua Yang, Ciyu Kahlert, Günther Ghani, Marvi Király, Nikolett Boratkó, Anita Uray, Karen Dittmar, Gunnar Tar, Krisztina Biomolecules Article The Blm10/PA200 family of proteasome activators modulates the peptidase activity of the core particle (20S CP). They participate in opening the 20S CP gate, thus facilitating the degradation of unstructured proteins such as tau and Dnm1 in a ubiquitin- and ATP-independent manner. Furthermore, PA200 also participates in the degradation of acetylated histones. In our study, we use a combination of yeast and human cell systems to investigate the role of Blm10/PA200 in the degradation of N-terminal Huntingtin fragments (N-Htt). We demonstrate that the human PA200 binds to N-Htt. The loss of Blm10 in yeast or PA200 in human cells results in increased mutant N-Htt aggregate formation and elevated cellular toxicity. Furthermore, Blm10 in vitro accelerates the proteasomal degradation of soluble N-Htt. Collectively, our data suggest N-Htt as a new substrate for Blm10/PA200-proteasomes and point to new approaches in Huntington’s disease (HD) research. MDPI 2020-11-20 /pmc/articles/PMC7699873/ /pubmed/33233776 http://dx.doi.org/10.3390/biom10111581 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Aladdin, Azzam Yao, Yanhua Yang, Ciyu Kahlert, Günther Ghani, Marvi Király, Nikolett Boratkó, Anita Uray, Karen Dittmar, Gunnar Tar, Krisztina The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin |
title | The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin |
title_full | The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin |
title_fullStr | The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin |
title_full_unstemmed | The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin |
title_short | The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin |
title_sort | proteasome activators blm10/pa200 enhance the proteasomal degradation of n-terminal huntingtin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699873/ https://www.ncbi.nlm.nih.gov/pubmed/33233776 http://dx.doi.org/10.3390/biom10111581 |
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