Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28

In embryonic stem cells, removal of oxidatively damaged proteins is triggered upon the first signs of cell fate specification but the underlying mechanism is not known. Here, we report that this phase of differentiation encompasses an unexpected induction of genes encoding the proteasome activator P...

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Autores principales: Hernebring, Malin, Fredriksson, Åsa, Liljevald, Maria, Cvijovic, Marija, Norrman, Karin, Wiseman, John, Semb, Henrik, Nyström, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587881/
https://www.ncbi.nlm.nih.gov/pubmed/23459332
http://dx.doi.org/10.1038/srep01381
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author Hernebring, Malin
Fredriksson, Åsa
Liljevald, Maria
Cvijovic, Marija
Norrman, Karin
Wiseman, John
Semb, Henrik
Nyström, Thomas
author_facet Hernebring, Malin
Fredriksson, Åsa
Liljevald, Maria
Cvijovic, Marija
Norrman, Karin
Wiseman, John
Semb, Henrik
Nyström, Thomas
author_sort Hernebring, Malin
collection PubMed
description In embryonic stem cells, removal of oxidatively damaged proteins is triggered upon the first signs of cell fate specification but the underlying mechanism is not known. Here, we report that this phase of differentiation encompasses an unexpected induction of genes encoding the proteasome activator PA28αβ (11S), subunits of the immunoproteasome (20Si), and the 20Si regulator TNFα. This induction is accompanied by assembly of mature PA28-20S(i) proteasomes and elevated proteasome activity. Inhibiting accumulation of PA28α using miRNA counteracted the removal of damaged proteins demonstrating that PA28αβ has a hitherto unidentified role required for resetting the levels of protein damage at the transition from self-renewal to cell differentiation.
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spelling pubmed-35878812013-03-05 Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28 Hernebring, Malin Fredriksson, Åsa Liljevald, Maria Cvijovic, Marija Norrman, Karin Wiseman, John Semb, Henrik Nyström, Thomas Sci Rep Article In embryonic stem cells, removal of oxidatively damaged proteins is triggered upon the first signs of cell fate specification but the underlying mechanism is not known. Here, we report that this phase of differentiation encompasses an unexpected induction of genes encoding the proteasome activator PA28αβ (11S), subunits of the immunoproteasome (20Si), and the 20Si regulator TNFα. This induction is accompanied by assembly of mature PA28-20S(i) proteasomes and elevated proteasome activity. Inhibiting accumulation of PA28α using miRNA counteracted the removal of damaged proteins demonstrating that PA28αβ has a hitherto unidentified role required for resetting the levels of protein damage at the transition from self-renewal to cell differentiation. Nature Publishing Group 2013-03-05 /pmc/articles/PMC3587881/ /pubmed/23459332 http://dx.doi.org/10.1038/srep01381 Text en Copyright © 2013, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareALike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Article
Hernebring, Malin
Fredriksson, Åsa
Liljevald, Maria
Cvijovic, Marija
Norrman, Karin
Wiseman, John
Semb, Henrik
Nyström, Thomas
Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
title Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
title_full Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
title_fullStr Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
title_full_unstemmed Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
title_short Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
title_sort removal of damaged proteins during es cell fate specification requires the proteasome activator pa28
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587881/
https://www.ncbi.nlm.nih.gov/pubmed/23459332
http://dx.doi.org/10.1038/srep01381
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