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Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression

Hsp70 proteins represent a family of chaperones that regulate cellular homeostasis and are required for cancer cell survival. However, their function and regulation in mitosis remain unknown. In this paper, we show that the major inducible cytoplasmic Hsp70 isoform, Hsp72, is required for assembly o...

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Autores principales: O’Regan, Laura, Sampson, Josephina, Richards, Mark W., Knebel, Axel, Roth, Daniel, Hood, Fiona E., Straube, Anne, Royle, Stephen J., Bayliss, Richard, Fry, Andrew M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427782/
https://www.ncbi.nlm.nih.gov/pubmed/25940345
http://dx.doi.org/10.1083/jcb.201409151
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author O’Regan, Laura
Sampson, Josephina
Richards, Mark W.
Knebel, Axel
Roth, Daniel
Hood, Fiona E.
Straube, Anne
Royle, Stephen J.
Bayliss, Richard
Fry, Andrew M.
author_facet O’Regan, Laura
Sampson, Josephina
Richards, Mark W.
Knebel, Axel
Roth, Daniel
Hood, Fiona E.
Straube, Anne
Royle, Stephen J.
Bayliss, Richard
Fry, Andrew M.
author_sort O’Regan, Laura
collection PubMed
description Hsp70 proteins represent a family of chaperones that regulate cellular homeostasis and are required for cancer cell survival. However, their function and regulation in mitosis remain unknown. In this paper, we show that the major inducible cytoplasmic Hsp70 isoform, Hsp72, is required for assembly of a robust bipolar spindle capable of efficient chromosome congression. Mechanistically, Hsp72 associates with the K-fiber–stabilizing proteins, ch-TOG and TACC3, and promotes their interaction with each other and recruitment to spindle microtubules (MTs). Targeting of Hsp72 to the mitotic spindle is dependent on phosphorylation at Thr-66 within its nucleotide-binding domain by the Nek6 kinase. Phosphorylated Hsp72 concentrates on spindle poles and sites of MT–kinetochore attachment. A phosphomimetic Hsp72 mutant rescued defects in K-fiber assembly, ch-TOG/TACC3 recruitment and mitotic progression that also resulted from Nek6 depletion. We therefore propose that Nek6 facilitates association of Hsp72 with the mitotic spindle, where it promotes stable K-fiber assembly through recruitment of the ch-TOG–TACC3 complex.
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spelling pubmed-44277822015-11-11 Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression O’Regan, Laura Sampson, Josephina Richards, Mark W. Knebel, Axel Roth, Daniel Hood, Fiona E. Straube, Anne Royle, Stephen J. Bayliss, Richard Fry, Andrew M. J Cell Biol Research Articles Hsp70 proteins represent a family of chaperones that regulate cellular homeostasis and are required for cancer cell survival. However, their function and regulation in mitosis remain unknown. In this paper, we show that the major inducible cytoplasmic Hsp70 isoform, Hsp72, is required for assembly of a robust bipolar spindle capable of efficient chromosome congression. Mechanistically, Hsp72 associates with the K-fiber–stabilizing proteins, ch-TOG and TACC3, and promotes their interaction with each other and recruitment to spindle microtubules (MTs). Targeting of Hsp72 to the mitotic spindle is dependent on phosphorylation at Thr-66 within its nucleotide-binding domain by the Nek6 kinase. Phosphorylated Hsp72 concentrates on spindle poles and sites of MT–kinetochore attachment. A phosphomimetic Hsp72 mutant rescued defects in K-fiber assembly, ch-TOG/TACC3 recruitment and mitotic progression that also resulted from Nek6 depletion. We therefore propose that Nek6 facilitates association of Hsp72 with the mitotic spindle, where it promotes stable K-fiber assembly through recruitment of the ch-TOG–TACC3 complex. The Rockefeller University Press 2015-05-11 /pmc/articles/PMC4427782/ /pubmed/25940345 http://dx.doi.org/10.1083/jcb.201409151 Text en © 2015 O’Regan et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
O’Regan, Laura
Sampson, Josephina
Richards, Mark W.
Knebel, Axel
Roth, Daniel
Hood, Fiona E.
Straube, Anne
Royle, Stephen J.
Bayliss, Richard
Fry, Andrew M.
Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression
title Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression
title_full Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression
title_fullStr Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression
title_full_unstemmed Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression
title_short Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression
title_sort hsp72 is targeted to the mitotic spindle by nek6 to promote k-fiber assembly and mitotic progression
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427782/
https://www.ncbi.nlm.nih.gov/pubmed/25940345
http://dx.doi.org/10.1083/jcb.201409151
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