A novel function of Saccharomyces cerevisiae CDC5 in cytokinesis.

A novel function of Saccharomyces cerevisiae CDC5 in cytokinesis.
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DOI:
10.1083/jcb.152.3.451
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发表时间:
2001-02-05
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Lee KS
Lee KS
中科院分区:
其他
文献类型:
--
作者:
Song S;Lee KS

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有丝分裂的退出与胞质分裂的及时启动相协调,是确保细胞分裂前完成有丝分裂的关键。酿酒酵母Polo激酶CDC5的功能是导致有丝分裂周期蛋白Clb2的降解,从而允许有丝分裂退出。在这里,我们提供了证据,CDC5也在调节细胞质分裂中发挥作用,并且这一事件需要一个完整的Polo-box,这是CDC5的非催化COOH末端结构域中的一个保守基序。CDC5功能的耗尽导致胞质分裂停止。过表达CDC5(CDC5ΔN)的COOH端结构域,但不表达相应的Polo-box突变体,导致细胞连接。这些细胞共用细胞质,隔膜不完整,并具有异常的隔素环结构。提供更多的内源性CDC5拷贝可以补救这种表型,这表明胞质分裂受到显性负向抑制。CDC5与Septins(CDC11和CDC12)之间的Polo盒依赖的相互作用,以及显性负的CDC5ΔN与Cyk2/Hof1或Myo1之间的遗传相互作用表明,CDC5ΔN与Septins之间的直接相互作用导致了Cyk2/Hof1和Myo1介导的细胞动力学途径的抑制。因此,我们认为,CDC5可能通过参与后期促进复合体激活和Polo盒依赖的细胞动力学途径来协调有丝分裂退出和胞质分裂。
Coordination of mitotic exit with timely initiation of cytokinesis is critical to ensure completion of mitotic events before cell division. The Saccharomyces cerevisiae polo kinase Cdc5 functions in a pathway leading to the degradation of mitotic cyclin Clb2, thereby permitting mitotic exit. Here we provide evidence that Cdc5 also plays a role in regulating cytokinesis and that an intact polo-box, a conserved motif in the noncatalytic COOH-terminal domain of Cdc5, is required for this event. Depletion of Cdc5 function leads to an arrest in cytokinesis. Overexpression of the COOH-terminal domain of Cdc5 (cdc5ΔN), but not the corresponding polo-box mutant, resulted in connected cells. These cells shared cytoplasms with incomplete septa, and possessed aberrant septin ring structures. Provision of additional copies of endogenous CDC5 remedied this phenotype, suggesting a dominant-negative inhibition of cytokinesis. The polo-box–dependent interactions between Cdc5 and septins (Cdc11 and Cdc12) and genetic interactions between the dominant-negative cdc5ΔN and Cyk2/Hof1 or Myo1 suggest that direct interactions between cdc5ΔN and septins resulted in inhibition of Cyk2/Hof1- and Myo1-mediated cytokinetic pathways. Thus, we propose that Cdc5 may coordinate mitotic exit with cytokinesis by participating in both anaphase promoting complex activation and a polo-box–dependent cytokinetic pathway.
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