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Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation
Heat shock response is characterized by the induction of heat shock proteins (HSPs), which facilitate protein folding, and non-HSP proteins with diverse functions, including protein degradation, and is regulated by heat shock factors (HSFs). HSF1 is a master regulator of HSP expression during heat s...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183013/ https://www.ncbi.nlm.nih.gov/pubmed/21813737 http://dx.doi.org/10.1091/mbc.E11-04-0330 |
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author | Shinkawa, Toyohide Tan, Ke Fujimoto, Mitsuaki Hayashida, Naoki Yamamoto, Kaoru Takaki, Eiichi Takii, Ryosuke Prakasam, Ramachandran Inouye, Sachiye Mezger, Valerie Nakai, Akira |
author_facet | Shinkawa, Toyohide Tan, Ke Fujimoto, Mitsuaki Hayashida, Naoki Yamamoto, Kaoru Takaki, Eiichi Takii, Ryosuke Prakasam, Ramachandran Inouye, Sachiye Mezger, Valerie Nakai, Akira |
author_sort | Shinkawa, Toyohide |
collection | PubMed |
description | Heat shock response is characterized by the induction of heat shock proteins (HSPs), which facilitate protein folding, and non-HSP proteins with diverse functions, including protein degradation, and is regulated by heat shock factors (HSFs). HSF1 is a master regulator of HSP expression during heat shock in mammals, as is HSF3 in avians. HSF2 plays roles in development of the brain and reproductive organs. However, the fundamental roles of HSF2 in vertebrate cells have not been identified. Here we find that vertebrate HSF2 is activated during heat shock in the physiological range. HSF2 deficiency reduces threshold for chicken HSF3 or mouse HSF1 activation, resulting in increased HSP expression during mild heat shock. HSF2-null cells are more sensitive to sustained mild heat shock than wild-type cells, associated with the accumulation of ubiquitylated misfolded proteins. Furthermore, loss of HSF2 function increases the accumulation of aggregated polyglutamine protein and shortens the lifespan of R6/2 Huntington's disease mice, partly through αB-crystallin expression. These results identify HSF2 as a major regulator of proteostasis capacity against febrile-range thermal stress and suggest that HSF2 could be a promising therapeutic target for protein-misfolding diseases. |
format | Online Article Text |
id | pubmed-3183013 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-31830132011-12-16 Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation Shinkawa, Toyohide Tan, Ke Fujimoto, Mitsuaki Hayashida, Naoki Yamamoto, Kaoru Takaki, Eiichi Takii, Ryosuke Prakasam, Ramachandran Inouye, Sachiye Mezger, Valerie Nakai, Akira Mol Biol Cell Articles Heat shock response is characterized by the induction of heat shock proteins (HSPs), which facilitate protein folding, and non-HSP proteins with diverse functions, including protein degradation, and is regulated by heat shock factors (HSFs). HSF1 is a master regulator of HSP expression during heat shock in mammals, as is HSF3 in avians. HSF2 plays roles in development of the brain and reproductive organs. However, the fundamental roles of HSF2 in vertebrate cells have not been identified. Here we find that vertebrate HSF2 is activated during heat shock in the physiological range. HSF2 deficiency reduces threshold for chicken HSF3 or mouse HSF1 activation, resulting in increased HSP expression during mild heat shock. HSF2-null cells are more sensitive to sustained mild heat shock than wild-type cells, associated with the accumulation of ubiquitylated misfolded proteins. Furthermore, loss of HSF2 function increases the accumulation of aggregated polyglutamine protein and shortens the lifespan of R6/2 Huntington's disease mice, partly through αB-crystallin expression. These results identify HSF2 as a major regulator of proteostasis capacity against febrile-range thermal stress and suggest that HSF2 could be a promising therapeutic target for protein-misfolding diseases. The American Society for Cell Biology 2011-10-01 /pmc/articles/PMC3183013/ /pubmed/21813737 http://dx.doi.org/10.1091/mbc.E11-04-0330 Text en © 2011 Shinkawa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Shinkawa, Toyohide Tan, Ke Fujimoto, Mitsuaki Hayashida, Naoki Yamamoto, Kaoru Takaki, Eiichi Takii, Ryosuke Prakasam, Ramachandran Inouye, Sachiye Mezger, Valerie Nakai, Akira Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation |
title | Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation |
title_full | Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation |
title_fullStr | Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation |
title_full_unstemmed | Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation |
title_short | Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation |
title_sort | heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183013/ https://www.ncbi.nlm.nih.gov/pubmed/21813737 http://dx.doi.org/10.1091/mbc.E11-04-0330 |
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