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Hsp110 Chaperones Control Client Fate Determination in the Hsp70–Hsp90 Chaperone System

Heat shock protein 70 (Hsp70) plays a central role in protein homeostasis and quality control in conjunction with other chaperone machines, including Hsp90. The Hsp110 chaperone Sse1 promotes Hsp90 activity in yeast, and functions as a nucleotide exchange factor (NEF) for cytosolic Hsp70, but the pr...

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Autores principales: Mandal, Atin K., Gibney, Patrick A., Nillegoda, Nadinath B., Theodoraki, Maria A., Caplan, Avrom J., Morano, Kevin A.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861604/
https://www.ncbi.nlm.nih.gov/pubmed/20237159
http://dx.doi.org/10.1091/mbc.E09-09-0779
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author Mandal, Atin K.
Gibney, Patrick A.
Nillegoda, Nadinath B.
Theodoraki, Maria A.
Caplan, Avrom J.
Morano, Kevin A.
author_facet Mandal, Atin K.
Gibney, Patrick A.
Nillegoda, Nadinath B.
Theodoraki, Maria A.
Caplan, Avrom J.
Morano, Kevin A.
author_sort Mandal, Atin K.
collection PubMed
description Heat shock protein 70 (Hsp70) plays a central role in protein homeostasis and quality control in conjunction with other chaperone machines, including Hsp90. The Hsp110 chaperone Sse1 promotes Hsp90 activity in yeast, and functions as a nucleotide exchange factor (NEF) for cytosolic Hsp70, but the precise roles Sse1 plays in client maturation through the Hsp70–Hsp90 chaperone system are not fully understood. We find that upon pharmacological inhibition of Hsp90, a model protein kinase, Ste11ΔN, is rapidly degraded, whereas heterologously expressed glucocorticoid receptor (GR) remains stable. Hsp70 binding and nucleotide exchange by Sse1 was required for GR maturation and signaling through endogenous Ste11, as well as to promote Ste11ΔN degradation. Overexpression of another functional NEF partially compensated for loss of Sse1, whereas the paralog Sse2 fully restored GR maturation and Ste11ΔN degradation. Sse1 was required for ubiquitinylation of Ste11ΔN upon Hsp90 inhibition, providing a mechanistic explanation for its role in substrate degradation. Sse1/2 copurified with Hsp70 and other proteins comprising the “early-stage” Hsp90 complex, and was absent from “late-stage” Hsp90 complexes characterized by the presence of Sba1/p23. These findings support a model in which Hsp110 chaperones contribute significantly to the decision made by Hsp70 to fold or degrade a client protein.
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spelling pubmed-28616042010-07-16 Hsp110 Chaperones Control Client Fate Determination in the Hsp70–Hsp90 Chaperone System Mandal, Atin K. Gibney, Patrick A. Nillegoda, Nadinath B. Theodoraki, Maria A. Caplan, Avrom J. Morano, Kevin A. Mol Biol Cell Articles Heat shock protein 70 (Hsp70) plays a central role in protein homeostasis and quality control in conjunction with other chaperone machines, including Hsp90. The Hsp110 chaperone Sse1 promotes Hsp90 activity in yeast, and functions as a nucleotide exchange factor (NEF) for cytosolic Hsp70, but the precise roles Sse1 plays in client maturation through the Hsp70–Hsp90 chaperone system are not fully understood. We find that upon pharmacological inhibition of Hsp90, a model protein kinase, Ste11ΔN, is rapidly degraded, whereas heterologously expressed glucocorticoid receptor (GR) remains stable. Hsp70 binding and nucleotide exchange by Sse1 was required for GR maturation and signaling through endogenous Ste11, as well as to promote Ste11ΔN degradation. Overexpression of another functional NEF partially compensated for loss of Sse1, whereas the paralog Sse2 fully restored GR maturation and Ste11ΔN degradation. Sse1 was required for ubiquitinylation of Ste11ΔN upon Hsp90 inhibition, providing a mechanistic explanation for its role in substrate degradation. Sse1/2 copurified with Hsp70 and other proteins comprising the “early-stage” Hsp90 complex, and was absent from “late-stage” Hsp90 complexes characterized by the presence of Sba1/p23. These findings support a model in which Hsp110 chaperones contribute significantly to the decision made by Hsp70 to fold or degrade a client protein. The American Society for Cell Biology 2010-05-01 /pmc/articles/PMC2861604/ /pubmed/20237159 http://dx.doi.org/10.1091/mbc.E09-09-0779 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Mandal, Atin K.
Gibney, Patrick A.
Nillegoda, Nadinath B.
Theodoraki, Maria A.
Caplan, Avrom J.
Morano, Kevin A.
Hsp110 Chaperones Control Client Fate Determination in the Hsp70–Hsp90 Chaperone System
title Hsp110 Chaperones Control Client Fate Determination in the Hsp70–Hsp90 Chaperone System
title_full Hsp110 Chaperones Control Client Fate Determination in the Hsp70–Hsp90 Chaperone System
title_fullStr Hsp110 Chaperones Control Client Fate Determination in the Hsp70–Hsp90 Chaperone System
title_full_unstemmed Hsp110 Chaperones Control Client Fate Determination in the Hsp70–Hsp90 Chaperone System
title_short Hsp110 Chaperones Control Client Fate Determination in the Hsp70–Hsp90 Chaperone System
title_sort hsp110 chaperones control client fate determination in the hsp70–hsp90 chaperone system
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861604/
https://www.ncbi.nlm.nih.gov/pubmed/20237159
http://dx.doi.org/10.1091/mbc.E09-09-0779
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