Kin4 kinase delays mitotic exit in response to spindle alignment defect
Kin4 kinase delays mitotic exit in response to spindle alignment defect
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DOI：
10.1016/j.molcel.2005.05.030
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发表时间：
2005-07-22
期刊：
影响因子：
16
通讯作者：
Schiebel, E
中科院分区：
文献类型：
--
作者：
Pereira, G;Schiebel, E
对于许多极化细胞来说，有丝分裂纺锤体相对于极性轴的定位至关重要。这对于酵母来说尤其重要，因为胞质分裂的位点是预先确定的。因此，纺锤体位置检查点（SPOC）会延迟纺锤体位置错误的细胞的有丝分裂退出。 SPOC 的一个组成部分是 Bub2-Bfa1 复合物，它是有丝分裂出口网络 (MEN) 的抑制剂。在这里，我们证明 Kin4 激酶是 SPOC 的一个组成部分，因此对于延迟纺锤体错位细胞的细胞周期进程至关重要。当纺锤体方向正确时，Kin4 和 Bub2-Bfa1 不对称地定位到相对的纺锤体极体 (SPB)。然后，Bub2-Bfa1 在后期开始时被 Cdc5 polo 激酶抑制，这是有丝分裂退出的先决条件。为了响应主轴未对准，Kin4 和 Bub2-Bfa1 在两个 SPB 处聚集在一起。 Kin4 现在通过抵消 Cdc5 来维持 Bub2-Bfa1 活性，从而抑制有丝分裂退出。
For many polarized cells, it is critical that the mitotic spindle becomes positioned relative to the polarity axis. This is especially important in yeast, where the site of cytokinesis is predetermined. The spindle position checkpoint (SPOC) therefore delays mitotic exit of cells with a mispositioned spindle. One component of the SPOC is the Bub2-Bfa1 complex, an inhibitor of the mitotic exit network (MEN). Here, we show that the Kin4 kinase is a component of the SPOC and as such is essential to delay cell cycle progression of cells with a misaligned spindle. When spindles are correctly oriented, Kin4 and Bub2-Bfa1 are asymmetrically localized to opposite spindle pole bodies (SPBs). Bub2-Bfa1 then becomes inhibited by Cdc5 polo kinase with anaphase onset, a prerequisite for mitotic exit. In response to spindle misalignment, Kin4 and Bub2-Bfa1 are brought together at both SPBs. Kin4 now maintains Bub2-Bfa1 activity by counteracting Cdc5, thereby inhibiting mitotic exit.