HSP70 regulates the function of mitotic centrosomes
- 30 April 2016
- journal article
- research article
- Published by Springer Nature in Cellular and Molecular Life Sciences
- Vol. 73 (20), 3949-3960
- https://doi.org/10.1007/s00018-016-2236-8
Abstract
To establish a functional bipolar mitotic spindle, the centrosome expands and matures, acquiring enhanced activities for microtubule (MT) nucleation and assembly at the onset of mitosis. However, the regulatory mechanisms of centrosome maturation and MT assembly from the matured centrosome are largely unknown. In this study, we showed that heat shock protein (HSP) 70 considerably accumulates at the mitotic centrosome during prometaphase to metaphase and is required for bipolar spindle assembly. Inhibition or depletion of HSP70 impaired the function of mitotic centrosome and disrupted MT nucleation and polymerization from the spindle pole, and may thus result in formation of abnormal mitotic spindles. In addition, HSP70 may associate with NEDD1 and γ-tubulin, two pericentriolar material (PCM) components essential for centrosome maturation and MT nucleation. Loss of HSP70 function disrupted the interaction between NEDD1 and γ-tubulin, and reduced their accumulation at the mitotic centrosome. Our results thus demonstrate a role for HSP70 in regulating centrosome integrity during mitosis, and indicate that HSP70 is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle.Keywords
Funding Information
- Academia Sinica
- Ministry of Science and Technology (NSC 102-2320-B-001-023-MY3)
This publication has 51 references indexed in Scilit:
- Mitotic catastrophe and cell death induced by depletion of centrosomal proteinsCell Death & Disease, 2013
- Hsp110 is required for spindle length controlThe Journal of cell biology, 2012
- C-terminal phosphorylation of Hsp70 and Hsp90 regulates alternate binding to co-chaperones CHIP and HOP to determine cellular protein folding/degradation balancesOncogene, 2012
- Inhibition of the Heat Shock Response by PI103 Enhances the Cytotoxicity of Arsenic TrioxideToxicological Sciences, 2012
- Pattern formation in centrosome assemblyCurrent Opinion in Cell Biology, 2012
- Integrins Regulate Microtubule Nucleating Activity of Centrosome through Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase/Extracellular Signal-regulated Kinase (MEK/ERK) SignalingJournal of Biological Chemistry, 2012
- PLK1 phosphorylation of pericentrin initiates centrosome maturation at the onset of mitosisThe Journal of cell biology, 2011
- Hsp70 stabilizes lysosomes and reverts Niemann–Pick disease-associated lysosomal pathologyNature, 2010
- A Small Molecule Inhibitor of Inducible Heat Shock Protein 70Molecular Cell, 2009
- Inhibition of Proteasome Activity Impairs Centrosome-dependent Microtubule Nucleation and OrganizationMolecular Biology of the Cell, 2008