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Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments
Hsp70 aids in protein folding and directs misfolded proteins to the cellular degradation machinery. We describe discrete roles of Hsp70,SSA1 as an important quality-control machinery that switches functions to ameliorate the cellular environment. SSA1 facilitates folding/maturation of newly synthesi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436772/ https://www.ncbi.nlm.nih.gov/pubmed/25739454 http://dx.doi.org/10.1091/mbc.E14-08-1262 |
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author | Roy, Joydeep Mitra, Sahana Sengupta, Kaushik Mandal, Atin K. |
author_facet | Roy, Joydeep Mitra, Sahana Sengupta, Kaushik Mandal, Atin K. |
author_sort | Roy, Joydeep |
collection | PubMed |
description | Hsp70 aids in protein folding and directs misfolded proteins to the cellular degradation machinery. We describe discrete roles of Hsp70,SSA1 as an important quality-control machinery that switches functions to ameliorate the cellular environment. SSA1 facilitates folding/maturation of newly synthesized protein kinases by aiding their phosphorylation process and also stimulates ubiquitylation and degradation of kinases in regular protein turnover or during stress when kinases are denatured or improperly folded. Significantly, while kinases accumulate as insoluble inclusions upon SSA1 inhibition, they form soluble inclusions upon Hsp90 inhibition or stress foci during heat stress. This suggests formation of inclusion-specific quality-control compartments under various stress conditions. Up-regulation of SSA1 results in complete removal of these inclusions by the proteasome. Elevation of the cellular SSA1 level accelerates kinase turnover and protects cells from proteotoxic stress. Upon overexpression, SSA1 targets heat-denatured kinases toward degradation, which could enable them to recover their functional state under physiological conditions. Thus active participation of SSA1 in the degradation of misfolded proteins establishes an essential role of Hsp70 in deciding client fate during stress. |
format | Online Article Text |
id | pubmed-4436772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-44367722015-07-16 Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments Roy, Joydeep Mitra, Sahana Sengupta, Kaushik Mandal, Atin K. Mol Biol Cell Articles Hsp70 aids in protein folding and directs misfolded proteins to the cellular degradation machinery. We describe discrete roles of Hsp70,SSA1 as an important quality-control machinery that switches functions to ameliorate the cellular environment. SSA1 facilitates folding/maturation of newly synthesized protein kinases by aiding their phosphorylation process and also stimulates ubiquitylation and degradation of kinases in regular protein turnover or during stress when kinases are denatured or improperly folded. Significantly, while kinases accumulate as insoluble inclusions upon SSA1 inhibition, they form soluble inclusions upon Hsp90 inhibition or stress foci during heat stress. This suggests formation of inclusion-specific quality-control compartments under various stress conditions. Up-regulation of SSA1 results in complete removal of these inclusions by the proteasome. Elevation of the cellular SSA1 level accelerates kinase turnover and protects cells from proteotoxic stress. Upon overexpression, SSA1 targets heat-denatured kinases toward degradation, which could enable them to recover their functional state under physiological conditions. Thus active participation of SSA1 in the degradation of misfolded proteins establishes an essential role of Hsp70 in deciding client fate during stress. The American Society for Cell Biology 2015-05-01 /pmc/articles/PMC4436772/ /pubmed/25739454 http://dx.doi.org/10.1091/mbc.E14-08-1262 Text en © 2015 Roy 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 for Cell Biology. |
spellingShingle | Articles Roy, Joydeep Mitra, Sahana Sengupta, Kaushik Mandal, Atin K. Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments |
title | Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments |
title_full | Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments |
title_fullStr | Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments |
title_full_unstemmed | Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments |
title_short | Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments |
title_sort | hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436772/ https://www.ncbi.nlm.nih.gov/pubmed/25739454 http://dx.doi.org/10.1091/mbc.E14-08-1262 |
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