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Nuclear polyglutamine-containing protein aggregates as active proteolytic centers
Protein aggregates and nuclear inclusions (NIs) containing components of the ubiquitin–proteasome system (UPS), expanded polyglutamine (polyQ) proteins, and transcriptional coactivators characterize cellular responses to stress and are hallmarks of neurodegenerative diseases. The biological function...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265588/ https://www.ncbi.nlm.nih.gov/pubmed/18283109 http://dx.doi.org/10.1083/jcb.200708131 |
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author | Chen, Min Singer, Lena Scharf, Andrea von Mikecz, Anna |
author_facet | Chen, Min Singer, Lena Scharf, Andrea von Mikecz, Anna |
author_sort | Chen, Min |
collection | PubMed |
description | Protein aggregates and nuclear inclusions (NIs) containing components of the ubiquitin–proteasome system (UPS), expanded polyglutamine (polyQ) proteins, and transcriptional coactivators characterize cellular responses to stress and are hallmarks of neurodegenerative diseases. The biological function of polyQ-containing aggregates is unknown. To analyze proteasomal activity within such aggregates, we present a nanoparticle (NP)-based method that enables controlled induction of sodium dodecyl sulfate–resistant inclusions of endogenous nuclear proteins while normal regulatory mechanisms remain in place. Consistent with the idea that the UPS maintains quality control, inhibition of proteasomal proteolysis promotes extra large protein aggregates (1.4–2 μm), whereas formation of NP-induced NIs is found to be inversely correlated to proteasome activation. We show that global proteasomal proteolysis increases in NP-treated nuclei and, on the local level, a subpopulation of NIs overlaps with focal domains of proteasome-dependent protein degradation. These results suggest that inclusions in the nucleus constitute active proteolysis modules that may serve to concentrate and decompose damaged, malfolded, or misplaced proteins. |
format | Text |
id | pubmed-2265588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22655882008-08-25 Nuclear polyglutamine-containing protein aggregates as active proteolytic centers Chen, Min Singer, Lena Scharf, Andrea von Mikecz, Anna J Cell Biol Research Articles Protein aggregates and nuclear inclusions (NIs) containing components of the ubiquitin–proteasome system (UPS), expanded polyglutamine (polyQ) proteins, and transcriptional coactivators characterize cellular responses to stress and are hallmarks of neurodegenerative diseases. The biological function of polyQ-containing aggregates is unknown. To analyze proteasomal activity within such aggregates, we present a nanoparticle (NP)-based method that enables controlled induction of sodium dodecyl sulfate–resistant inclusions of endogenous nuclear proteins while normal regulatory mechanisms remain in place. Consistent with the idea that the UPS maintains quality control, inhibition of proteasomal proteolysis promotes extra large protein aggregates (1.4–2 μm), whereas formation of NP-induced NIs is found to be inversely correlated to proteasome activation. We show that global proteasomal proteolysis increases in NP-treated nuclei and, on the local level, a subpopulation of NIs overlaps with focal domains of proteasome-dependent protein degradation. These results suggest that inclusions in the nucleus constitute active proteolysis modules that may serve to concentrate and decompose damaged, malfolded, or misplaced proteins. The Rockefeller University Press 2008-02-25 /pmc/articles/PMC2265588/ /pubmed/18283109 http://dx.doi.org/10.1083/jcb.200708131 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Chen, Min Singer, Lena Scharf, Andrea von Mikecz, Anna Nuclear polyglutamine-containing protein aggregates as active proteolytic centers |
title | Nuclear polyglutamine-containing protein aggregates as active proteolytic centers |
title_full | Nuclear polyglutamine-containing protein aggregates as active proteolytic centers |
title_fullStr | Nuclear polyglutamine-containing protein aggregates as active proteolytic centers |
title_full_unstemmed | Nuclear polyglutamine-containing protein aggregates as active proteolytic centers |
title_short | Nuclear polyglutamine-containing protein aggregates as active proteolytic centers |
title_sort | nuclear polyglutamine-containing protein aggregates as active proteolytic centers |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265588/ https://www.ncbi.nlm.nih.gov/pubmed/18283109 http://dx.doi.org/10.1083/jcb.200708131 |
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