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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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journal contribution
posted on 13.05.2015, 14:09 by Laura O'Regan, Josephina Sampson, Mark W. Richards, A. Knebel, D. Roth, F. E. Hood, A. Straube, S. J. Royle, Richard Bayliss, Andrew M. Fry
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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Citation

Journal of Cell Biology 2015 vol. 209 no. 3 349-358

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Biochemistry

Version

VoR (Version of Record)

Published in

Journal of Cell Biology 2015 vol. 209 no. 3 349-358

Publisher

Rockefeller University Press

issn

0021-9525

eissn

1540-8140

Copyright date

2015

Available date

13/05/2015

Publisher version

http://jcb.rupress.org/content/209/3/349

Notes

Supplemental material can be found at: http://jcb.rupress.org/content/suppl/2015/04/30/jcb.201409151.DC1.html

Language

en

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