Heat shock protein 90 regulates the metaphase-anaphase transition in a polo-like kinase-dependent manner
Heat shock protein 90 regulates the metaphase-anaphase transition in a polo-like kinase-dependent manner
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DOI：
10.1158/0008-5472.can-03-2214
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发表时间：
2004-08-01
期刊：
影响因子：
11.2
通讯作者：
de Cárcer, G
中科院分区：
文献类型：
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作者：
de Cárcer, G
我们以前已经证明，分子伴侣热休克蛋白90(Hsp90)是正常中心体功能所必需的。事实上，这种Hsp90功能似乎反映在Polo样激酶的稳定性中。抑制Hsp90可导致HeLa细胞周期停滞于G2期或中期-后期转变。在这里，我们表明，这种抑制导致后期促进复合体或环体通过去磷酸化和诱导纺锤体组装检查点失活。抑制HSP90可以抑制两种主要的有丝分裂酶，Polo-like kinase1(Plk1)和cdc2。有趣的是，这种有丝分裂停滞并不发生在11490和plk1不相关的某些肿瘤细胞系中。这些细胞能够成功地进行有丝分裂，并具有活性的Plk1，尽管Hsp90失活。因此，Hsp90似乎依赖于它与Plk1的联系来调节有丝分裂的完成。
We have shown previously that the molecular chaperone heat shock protein 90 (Hsp90) is required for a proper centrosome function. Indeed, this Hsp90 function seems to be reflected in Polo-like kinase stability. Inhibition of Hsp90 in HeLa cells results in cell cycle arrest either in G2 stage or at the metaphase-anaphase transition. Here, we show that this inhibition leads to inactivation of the anaphase-promoting complex or cyclosome by both dephosphorylation and induction of the spindle assembly checkpoint. Hsp90 inhibition compromises two of the main mitotic kinases, Polo-like kinase 1 (Plk1) and cdc2. Interestingly, this mitotic arrest does not occur in certain tumor cell lines where 11490 and Plk1 are not associated. Those cells are able to process mitosis successfully and have an active Plk1 despite Hsp90 inactivation. Therefore, it seems that Hsp90 regulates completion of mitosis depending on its association with Plk1.