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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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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. |
format | Online Article Text |
id | pubmed-4427782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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