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HSP70 colocalizes with PLK1 at the centrosome and disturbs spindle dynamics in cells arrested in mitosis by arsenic trioxide
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  • 作者:Yu-Ju Chen (1) (2)
    Kuo-Chu Lai (3)
    Hsiao-Hui Kuo (4)
    Lu-Ping Chow (2)
    Ling-Huei Yih (4)
    Te-Chang Lee (1)
  • 关键词:Arsenic trioxide ; Mitotic arrest ; HSP70 ; PLK1 ; Centrosome ; Mitotic spindle
  • 刊名:Archives of Toxicology
  • 出版年:2014
  • 出版时间:September 2014
  • 年:2014
  • 卷:88
  • 期:9
  • 页码:1711-1723
  • 全文大小:1,216 KB
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  • 作者单位:Yu-Ju Chen (1) (2)
    Kuo-Chu Lai (3)
    Hsiao-Hui Kuo (4)
    Lu-Ping Chow (2)
    Ling-Huei Yih (4)
    Te-Chang Lee (1)

    1. Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan
    2. Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan
    3. Department of Pharmacology, Tzu Chi University, Hualien, 97004, Taiwan
    4. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan
  • ISSN:1432-0738
文摘
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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