Hwa Lim Hong, Yeong Foong May, Surana Uttam
Institute of Molecular and Cell Biology, Singapore 117609.
Mol Biol Cell. 2003 Nov;14(11):4734-43. doi: 10.1091/mbc.e03-04-0238. Epub 2003 Aug 22.
Chromosome segregation, mitotic exit, and cytokinesis are executed in this order during mitosis. Although a scheme coordinating sister chromatid separation and initiation of mitotic exit has been proposed, the mechanism that temporally links the onset of cytokinesis to mitotic exit is not known. Exit from mitosis is regulated by the mitotic exit network (MEN), which includes a GTPase (Tem1) and various kinases (Cdc15, Cdc5, Dbf2, and Dbf20). Here, we show that Dbf2 and Dbf20 functions are necessary for the execution of cytokinesis. Relocalization of these proteins from spindle pole bodies to mother daughter neck seems to be necessary for this role because cdc15-2 mutant cells, though capable of exiting mitosis at semipermissive temperature, are unable to localize Dbf2 (and Dbf20) to the "neck" and fail to undergo cytokinesis. These cells can assemble and constrict the actomyosin ring normally but are incapable of forming a septum, suggesting that MEN components are critical for the initiation of septum formation. Interestingly, the spindle pole body to neck translocation of Dbf2 and Dbf20 is triggered by the inactivation of mitotic kinase. The requirement of kinase inactivation for translocation of MEN components to the division site thus provides a mechanism that renders mitotic exit a prerequisite for cytokinesis.
在有丝分裂过程中，染色体分离、有丝分裂退出和胞质分裂按此顺序进行。尽管已经提出了一种协调姐妹染色单体分离和有丝分裂退出起始的机制，但将胞质分裂起始与有丝分裂退出在时间上联系起来的机制尚不清楚。有丝分裂退出受有丝分裂退出网络（MEN）调控，该网络包括一种GTP酶（Tem1）和各种激酶（Cdc15、Cdc5、Dbf2和Dbf20）。在这里，我们表明Dbf2和Dbf20的功能对于胞质分裂的执行是必需的。这些蛋白质从纺锤极体重新定位到母-子颈部似乎是发挥此作用所必需的，因为cdc15-2突变细胞虽然能够在半允许温度下退出有丝分裂，但无法将Dbf2（和Dbf20）定位到“颈部”，并且无法进行胞质分裂。这些细胞能够正常组装和收缩肌动球蛋白环，但无法形成隔膜，这表明MEN组件对于隔膜形成的起始至关重要。有趣的是，Dbf2和Dbf20从纺锤极体到颈部的易位是由有丝分裂激酶的失活触发的。因此，MEN组件易位到分裂位点需要激酶失活，这提供了一种机制，使有丝分裂退出成为胞质分裂的先决条件。
