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

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O'Regan, L., Sampson, J., Richards, M. W., Knebel, A., Roth, Daniel, Hood, F. E., Straube, Anne, Royle, Stephen J., Bayliss, R. and Fry, A. M. (2015) Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression. The Journal of Cell Biology, Volume 209 (Number 3). pp. 349-358. doi:10.1083/jcb.201409151 ISSN 0021-9525.

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Official URL: http://dx.doi.org/10.1083/jcb.201409151

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Abstract

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.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Molecular chaperones, Heat shock proteins, Cancer--Treatment
Journal or Publication Title: The Journal of Cell Biology
Publisher: The Rockefeller University Press
ISSN: 0021-9525
Official Date: 4 May 2015
Dates:
DateEvent
4 May 2015Published
31 March 2015Accepted
30 September 2014Submitted
Volume: Volume 209
Number: Number 3
Number of Pages: 10
Page Range: pp. 349-358
DOI: 10.1083/jcb.201409151
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 15 July 2019
Date of first compliant Open Access: 15 July 2019
Funder: Worldwide Cancer Research (Organization), Cancer Research UK (CRUK), Wellcome Trust (London, England), Lister Institute of Preventive Medicine, Medical Research Council (Great Britain) (MRC), Hope Foundation for Cancer Research in Leicestershire and Rutland
Grant number: 13-0042 (Worldwide Cancer Research) ; C1362/A18081 (CRUK) ; C24461/A12772 (CRUK); C25425/A15182 (CRUK) ; 082828 (Wellcome Trust) ; 097828 (Wellcome Trust)

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