MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
J Cell Sci. 2022 Jan 15;135(2). doi: 10.1242/jcs.259273. Epub 2022 Jan 18.
The control of protein abundance is a fundamental regulatory mechanism during mitosis. The anaphase-promoting complex/cyclosome (APC/C) is the main protein ubiquitin ligase responsible for the temporal regulation of mitotic progression. It has been proposed that the APC/C might fulfil other functions, including assembly of the mitotic spindle. Here, we show that the APC/C localizes to centrosomes, the organizers of the eukaryotic microtubule cytoskeleton, specifically during mitosis. Recruitment of the APC/C to spindle poles requires the centrosomal protein Cep152, and we identified Cep152 as both an APC/C interaction partner and an APC/C substrate. Previous studies have shown that Cep152 forms a complex with Cep57 and Cep63. The APC/C-mediated ubiquitylation of Cep152 at the centrosome releases Cep57 from this inhibitory complex and enables its interaction with pericentrin, a critical step in promoting microtubule nucleation. Thus, our study extends the function of the APC/C from being a regulator of mitosis to also acting as a positive governor of spindle assembly. The APC/C thereby integrates control of these two important processes in a temporal manner.
蛋白质丰度的控制是有丝分裂过程中的一种基本调控机制。后期促进复合物/周期蛋白体（APC/C）是负责有丝分裂进程的时间调节的主要蛋白质泛素连接酶。有人提出，APC/C 可能还具有其他功能，包括有丝分裂纺锤体的组装。在这里，我们发现 APC/C 定位于中心体，即真核微管细胞骨架的组织者，特别是在有丝分裂期间。APC/C 招募到纺锤体极需要中心体蛋白 Cep152，我们确定 Cep152 既是 APC/C 的相互作用伙伴，也是 APC/C 的底物。先前的研究表明，Cep152 与 Cep57 和 Cep63 形成复合物。APC/C 在中心体上对 Cep152 的泛素化修饰将 Cep57 从这个抑制性复合物中释放出来，并使其与中心粒蛋白（pericentrin）相互作用，这是促进微管成核的关键步骤。因此，我们的研究将 APC/C 的功能从有丝分裂的调节者扩展到纺锤体组装的积极调控者。APC/C 以时间方式整合了这两个重要过程的控制。
