Marangos Petros, Carroll John
Department of Cell and Developmental Biology, Division of Biosciences, University College London, Gower Street, London, WC1E 6BT, UK.
Nat Cell Biol. 2008 Apr;10(4):445-51. doi: 10.1038/ncb1707. Epub 2008 Mar 23.
Timely progression into mitosis is necessary for normal cell division. This transition is sensitive to the levels of cyclin B, the regulatory subunit of the master mitotic kinase, Cdk1. Cyclin B accumulates during G2 and prophase when its rate of destruction by the anaphase promoting complex (APC) is low. Securin is also an APC substrate and is known for its role in inactivating the cohesin-cleaving enzyme, separase, until the metaphase to anaphase transition. Here we show that securin has an additional role in cell-cycle regulation, that of modulating the timing of entry into M-phase. In mouse oocytes, excess securin caused stabilization of cyclin B and precocious entry into M-phase. Depletion of securin increased cyclin B degradation, resulting in delayed progression into M-phase. This effect required APC activity and was reversed by expression of wild-type securin. These data reveal a role for securin at the G2-M transition and suggest a more general mechanism whereby physiological levels of co-competing APC substrates function in modulating the timing of cell-cycle transitions.
及时进入有丝分裂对于正常细胞分裂至关重要。这种转变对细胞周期蛋白B的水平敏感，细胞周期蛋白B是主要有丝分裂激酶Cdk1的调节亚基。细胞周期蛋白B在G2期和前期积累，此时其被后期促进复合物（APC）破坏的速率较低。securin也是APC的底物，并且因其在使黏连蛋白切割酶分离酶失活方面的作用而闻名，直到中期到后期的转变。在这里，我们表明securin在细胞周期调节中具有额外的作用，即调节进入M期的时间。在小鼠卵母细胞中，过量的securin导致细胞周期蛋白B的稳定并过早进入M期。securin的缺失增加了细胞周期蛋白B的降解，导致进入M期的进程延迟。这种效应需要APC活性，并且通过野生型securin的表达得以逆转。这些数据揭示了securin在G2-M转变中的作用，并提出了一种更普遍的机制，即共同竞争的APC底物的生理水平在调节细胞周期转变的时间方面发挥作用。
