Kim Taekyung, Lara-Gonzalez Pablo, Prevo Bram, Meitinger Franz, Cheerambathur Dhanya K, Oegema Karen, Desai Arshad
Ludwig Institute for Cancer Research, San Diego, California 92093, USA.
Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA.
Genes Dev. 2017 Jun 1;31(11):1089-1094. doi: 10.1101/gad.302067.117. Epub 2017 Jul 11.
Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the APC/C. Here, we show that flux of Cdc20 through kinetochores also accelerates mitotic exit by promoting its dephosphorylation by kinetochore-localized protein phosphatase 1, which allows Cdc20 to activate the APC/C. Both APC/C activation and inhibition depend on Cdc20 fluxing through the same binding site at kinetochores. The microtubule attachment status of kinetochores therefore optimizes mitotic duration by controlling the balance between opposing Cdc20 fates.
有丝分裂持续时间由与共激活因子Cdc20结合的后期促进复合体/细胞周期体（APC/C）的激活所决定。动粒是染色体上与微管相互作用的机制，当未与纺锤体微管连接时，通过产生一种抑制APC/C的含Cdc20复合体来抑制有丝分裂退出。在此，我们表明，Cdc20通过动粒的通量还通过促进动粒定位的蛋白磷酸酶1使其去磷酸化来加速有丝分裂退出，这使得Cdc20能够激活APC/C。APC/C的激活和抑制都取决于Cdc20通过动粒上相同结合位点的通量。因此，动粒的微管附着状态通过控制相反的Cdc20命运之间的平衡来优化有丝分裂持续时间。
