Archives of Toxicology

, Volume 88, Issue 9, pp 1711–1723 | Cite as

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

Molecular Toxicology


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.


Arsenic trioxide Mitotic arrest HSP70 PLK1 Centrosome Mitotic spindle 



Arsenic trioxide


Heat shock protein 70






Polo-like kinase 1



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.

Supplementary material

204_2014_1222_MOESM1_ESM.pdf (126 kb)
Supplementary material 1 (PDF 126 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Institute of Biomedical SciencesAcademia SinicaTaipeiTaiwan
  2. 2.Graduate Institute of Biochemistry and Molecular Biology, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  3. 3.Department of PharmacologyTzu Chi UniversityHualienTaiwan
  4. 4.Institute of Cellular and Organismic BiologyAcademia SinicaTaipeiTaiwan

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