Heat shock‐induced mitotic arrest requires heat shock protein 105 for the activation of spindle assembly checkpoint

  • Ayana Kakihana
    Department of Biochemistry and Molecular BiologyKyoto Pharmaceutical University Kyoto Japan
  • Yui Oto
    Department of Biochemistry and Molecular BiologyKyoto Pharmaceutical University Kyoto Japan
  • Youhei Saito
    Department of Biochemistry and Molecular BiologyKyoto Pharmaceutical University Kyoto Japan
  • Yuji Nakayama
    Department of Biochemistry and Molecular BiologyKyoto Pharmaceutical University Kyoto Japan

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Heat shock causes proteotoxic stress that induces various cellular responses, including delayed mitotic progression and the generation of an aberrant number of chromosomes. In this study, heat shock delayed the onset of anaphase by increasing the number of misoriented cells, accompanied by the kinetochore localization of budding uninhibited by benzimidazole-related (BubR)1 in a monopolar spindle (Mps)1-dependent manner. The mitotic delay was canceled by knockdown of mitotic arrest defect (Mad)2. Knockdown of heat shock protein (Hsp)105 partially abrogated the mitotic delay with the loss of the kinetochore localization of BubR1 under heat shock conditions and accelerated mitotic progression under nonstressed conditions. Consistent with this result, Hsp105 knockdown increased the number of anaphase cells with lagging chromosomes, through mitotic slippage, and decreased taxol sensitivity more than Mad2 knockdown. Hsp105 was coprecipitated with cell division cycle (Cdc)20 in an Mps1-dependent manner; however, its knockdown did not affect coprecipitation of Mad2 and BubR1 with Cdc20. We propose that heat shock delays the onset of anaphase via the activation of the spindle assembly checkpoint (SAC). Hsp105 prevents abnormal cell division by contributing to SAC activation under heat shock and nonstressed conditions by interacting with Cdc20 but not affecting formation of the mitotic checkpoint complex.-Kakihana, A., Oto, Y., Saito, Y., Nakayama, Y. Heat shock-induced mitotic arrest requires heat shock protein 105 for the activation of spindle assembly checkpoint.

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