Kamieniecki Rebecca J, Liu Li, Dawson Dean S
Department of Microbiology and Molecular Biology,Sackler School of Biomedical Sciences, Tufts University, Boston, Massachusettes 02111, USA.
Cell Cycle. 2005 Aug;4(8):1093-8. Epub 2005 Aug 23.
Exit from mitosis is regulated by Cdc14, which plays an essential role in triggering cyclin-dependent kinase inactivation. Throughout most of the cell cycle, Cdc14 is sequestered in the nucleolus where it remains inactive. After the completion of anaphase, an essential signaling cascade, named the Mitotic Exit Network, or MEN, promotes Cdc14 release. Cdc14 is also released from the nucleolus in early anaphase by another, nonessential, pathway called FEAR (CdcFourteen Early Anaphase Release). Separase (Esp1), polo kinase (Cdc5), the kinetochore protein Slk19, and Spo12, whose molecular function remains unknown, have been identified as members of the FEAR pathway. In meiosis, mutations in CDC14 and its FEAR pathway regulators, CDC5, SLK19, and SPO12, all result it asci that contain only two diploid spores because of a defect in the ability to exit meiosis I. Thus although the FEAR pathway is dispensible for mitotic exit, it is essential for meiosis I exit. The way that the genes of the Mitotic Exit Network contribute to coordinating meiotic progression is less clear. Here, we explore this issue. Our results demonstrate that the orderly transition from meiosis I to meiosis II is accomplished by eliminating MEN function and using the FEAR pathway to modulate cyclin dependent kinase activity, in part through the actions of SIC1.
有丝分裂的退出由Cdc14调控，它在触发细胞周期蛋白依赖性激酶失活中起关键作用。在细胞周期的大部分时间里，Cdc14被隔离在核仁中，处于无活性状态。后期完成后，一个名为有丝分裂退出网络（MEN）的重要信号级联反应促进Cdc14的释放。在后期早期，Cdc14也通过另一条非必需途径从核仁中释放，该途径称为FEAR（Cdc14早期后期释放）。分离酶（Esp1）、polo激酶（Cdc5）、动粒蛋白Slk19和分子功能未知的Spo12已被确定为FEAR途径的成员。在减数分裂中，CDC14及其FEAR途径调节因子CDC5、SLK19和SPO12的突变，都会导致子囊仅含有两个二倍体孢子，因为减数分裂I退出能力存在缺陷。因此，尽管FEAR途径对于有丝分裂退出并非必需，但对于减数分裂I退出却是必不可少的。有丝分裂退出网络的基因如何协调减数分裂进程尚不清楚。在这里，我们探讨了这个问题。我们的结果表明，从减数分裂I到减数分裂II的有序转变是通过消除MEN功能并利用FEAR途径来调节细胞周期蛋白依赖性激酶活性来实现的，部分是通过SIC1的作用。
