Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/32269
Title: Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression.
Authors: O'Regan, Laura
Sampson, Josephina
Richards, Mark W.
Knebel, A.
Roth, D.
Hood, F. E.
Straube, A.
Royle, S. J.
Bayliss, Richard
Fry, Andrew M.
First Published: 4-May-2015
Publisher: Rockefeller University Press
Citation: Journal of Cell Biology 2015 vol. 209 no. 3 349-358
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.
DOI Link: 10.1083/jcb.201409151
ISSN: 0021-9525
eISSN: 1540-8140
Links: http://jcb.rupress.org/content/209/3/349
http://hdl.handle.net/2381/32269
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Archived with reference to SHERPA/RoMEO and publisher website. © 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/).
Description: Supplemental material can be found at: http://jcb.rupress.org/content/suppl/2015/04/30/jcb.201409151.DC1.html
Appears in Collections:Published Articles, Dept. of Biochemistry

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