Di Fiore Barbara, Davey Norman E, Hagting Anja, Izawa Daisuke, Mansfeld Jörg, Gibson Toby J, Pines Jonathon
The Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge, CB2 1QN, UK.
Department of Physiology and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
Dev Cell. 2015 Feb 9;32(3):358-372. doi: 10.1016/j.devcel.2015.01.003.
The anaphase-promoting complex or cyclosome (APC/C) is the ubiquitin ligase that regulates mitosis by targeting specific proteins for degradation at specific times under the control of the spindle assembly checkpoint (SAC). How the APC/C recognizes its different substrates is a key problem in the control of cell division. Here, we have identified the ABBA motif in cyclin A, BUBR1, BUB1, and Acm1, and we show that it binds to the APC/C coactivator CDC20. The ABBA motif in cyclin A is required for its proper degradation in prometaphase through competing with BUBR1 for the same site on CDC20. Moreover, the ABBA motifs in BUBR1 and BUB1 are necessary for the SAC to work at full strength and to recruit CDC20 to kinetochores. Thus, we have identified a conserved motif integral to the proper control of mitosis that connects APC/C substrate recognition with the SAC.
后期促进复合物或细胞周期体(APC/C)是一种泛素连接酶,在纺锤体组装检查点(SAC)的控制下,通过在特定时间靶向特定蛋白质进行降解来调节有丝分裂。APC/C如何识别其不同底物是细胞分裂控制中的一个关键问题。在这里,我们在细胞周期蛋白A、BUBR1、BUB1和Acm1中鉴定出了ABBA基序,并且我们表明它与APC/C共激活因子CDC20结合。细胞周期蛋白A中的ABBA基序通过与BUBR1竞争CDC20上的同一位点,在有丝分裂前期对其进行适当降解是必需的。此外,BUBR1和BUB1中的ABBA基序对于SAC充分发挥作用以及将CDC20招募到动粒是必需的。因此,我们已经鉴定出一个对有丝分裂的适当控制不可或缺的保守基序,它将APC/C底物识别与SAC联系起来。