CRUK Cell Division Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 4BX, UK.
Nat Cell Biol. 2012 Jun 10;14(7):738-45. doi: 10.1038/ncb2514.
Mitotic exit integrates the reversal of the phosphorylation events initiated by mitotic kinases with a controlled cytokinesis event that cleaves the cell in two. The mitotic exit network (MEN) of budding yeast regulates both processes, whereas the fission yeast equivalent, the septum initiation network (SIN), controls only the execution of cytokinesis. The components and architecture of the SIN and MEN are highly conserved. At present, it is assumed that the functions of the core SIN-MEN components are restricted to their characterized roles at the end of mitosis. We now show that the NDR (nuclear Dbf2-related) kinase component of the fission yeast SIN, Sid2-Mob1, acts independently of the other known SIN components in G2 phase of the cell cycle to control the timing of mitotic commitment. Sid2-Mob1 promotes mitotic commitment by directly activating the NIMA (Never In Mitosis)-related kinase Fin1. Fin1's activation promotes its own destruction, thereby making Fin1 activation a transient feature of G2 phase. This spike of Fin1 activation modulates the activity of the Pom1/Cdr1/Cdr2 geometry network towards Wee1.
有丝分裂退出将有丝分裂激酶引发的磷酸化事件的逆转与控制细胞分裂的有丝分裂事件结合在一起。芽殖酵母的有丝分裂退出网络（MEN）调节这两个过程，而裂殖酵母的等效物，隔膜起始网络（SIN），仅控制细胞分裂的执行。SIN 和 MEN 的组成部分和结构高度保守。目前，人们认为核心 SIN-MEN 成分的功能仅限于它们在有丝分裂末期的特征作用。我们现在表明，裂殖酵母 SIN 的 NDR（核 Dbf2 相关）激酶成分 Sid2-Mob1 在细胞周期的 G2 期独立于其他已知的 SIN 成分起作用，以控制有丝分裂承诺的时间。Sid2-Mob1 通过直接激活与 NIMA（Never In Mitosis）相关的激酶 Fin1 来促进有丝分裂承诺。Fin1 的激活促进其自身的破坏，从而使 Fin1 激活成为 G2 期的瞬态特征。这种 Fin1 激活的尖峰调节了 Pom1/Cdr1/Cdr2 几何网络对 Wee1 的活性。
