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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...

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Autores principales: Shinkawa, Toyohide, Tan, Ke, Fujimoto, Mitsuaki, Hayashida, Naoki, Yamamoto, Kaoru, Takaki, Eiichi, Takii, Ryosuke, Prakasam, Ramachandran, Inouye, Sachiye, Mezger, Valerie, Nakai, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
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.
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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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