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HSP70 colocalizes with PLK1 at the centrosome and disturbs spindle dynamics in cells arrested in mitosis by arsenic trioxide

  • Molecular Toxicology
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Abstract

Heat shock protein 70 (HSP70) has been shown to be a substrate of Polo-like kinase 1 (PLK1), and it prevents cells arrested in mitosis by arsenic trioxide (ATO) from dying. Here, we report that HSP70 participates in ATO-induced spindle elongation, which interferes with mitosis progression. Our results demonstrate that HSP70 and PLK1 colocalize at the centrosome in ATO-arrested mitotic cells. HSP70 located at the centrosome was found to be phosphorylated by PLK1 at Ser631 and Ser633. Moreover, unlike wild-type HSP70 (HSP70wt) and its phosphomimetic mutant (HSP70SS631,633DD), a phosphorylation-resistant mutant of HSP70 (HSP70SS631,633AA) failed to localize at the centrosome. ATO-induced spindle elongation was abolished in cells overexpressing HSP70SS631,633AA. Conversely, mitotic spindles in cells ectopically expressing HSP70SS631,633DD were more resistant to nocodazole-induced depolymerization than in those expressing HSP70wt or HSP70SS631,633AA. In addition, inhibition of PLK1 significantly reduced HSP70 phosphorylation and induced early onset of apoptosis in ATO-arrested mitotic cells. Taken together, our results indicate that PLK1-mediated phosphorylation and centrosomal localization of HSP70 may interfere with spindle dynamics and prevent apoptosis of ATO-arrested mitotic cells.

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Abbreviations

ATO:

Arsenic trioxide

HSP70:

Heat shock protein 70

MT:

Microtubule

PES:

2-Phenylethynesulfonamide

PLK1:

Polo-like kinase 1

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Acknowledgments

This work was supported in part by Academia Sinica and grants from the National Health Research Institutes (NHRI-EX96-9522BI to T.C.L.) and the National Science Council (NSC98-2320-B-001-002-MY3 to T.C.L., NSC98-2320-B-002-030 to L.P.C., and NSC99-2320-B-001-008-MY3 to L. H. Y.), Taiwan.

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Authors and Affiliations

  1. Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan

    Yu-Ju Chen & Te-Chang Lee

  2. Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan

    Yu-Ju Chen & Lu-Ping Chow

  3. Department of Pharmacology, Tzu Chi University, Hualien, 97004, Taiwan

    Kuo-Chu Lai

  4. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan

    Hsiao-Hui Kuo & Ling-Huei Yih

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  1. Yu-Ju Chen
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  2. Kuo-Chu Lai
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  3. Hsiao-Hui Kuo
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Correspondence to Ling-Huei Yih or Te-Chang Lee.

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Chen, YJ., Lai, KC., Kuo, HH. et al. HSP70 colocalizes with PLK1 at the centrosome and disturbs spindle dynamics in cells arrested in mitosis by arsenic trioxide. Arch Toxicol 88, 1711–1723 (2014). https://doi.org/10.1007/s00204-014-1222-x

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