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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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: | Date Event 4 May 2015 Published 31 March 2015 Accepted 30 September 2014 Submitted |
| 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 open licence) |
| 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) |
| URI: | https://wrap.warwick.ac.uk/70138/ |
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