a Institut Jacques Monod , UMR7592, CNRS, Université Paris Diderot, Sorbonne Paris Cité , Paris , France.
b Ecole Doctorale Structure et Dynamique des Systèmes Vivants (#577) , Univ Paris Sud, Université Paris-Saclay , Orsay , France.
Cell Cycle. 2018;17(17):2122-2133. doi: 10.1080/15384101.2018.1520569. Epub 2018 Sep 20.
In metazoans, the assembly of kinetochores on centrometric chromatin and the dismantling of nuclear pore complexes are processes that have to be tightly coordinated to ensure the proper assembly of the mitotic spindle and a successful mitosis. It is therefore noteworthy that these two macromolecular assemblies share a subset of constituents. One of these multifaceted components is Cenp-F, a protein implicated in cancer and developmental pathologies. During the cell cycle, Cenp-F localizes in multiple cellular structures including the nuclear envelope in late G2/early prophase and kinetochores throughout mitosis. We recently characterized the molecular determinants of Cenp-F interaction with Nup133, a structural nuclear pore constituent. In parallel with two other independent studies, we further elucidated the mechanisms governing Cenp-F kinetochore recruitment that mainly relies on its interaction with Bub1, with redundant contribution of Cenp-E upon acute microtubule depolymerisation. Here we synthesize the current literature regarding the dual location of Cenp-F at nuclear pores and kinetochores and extend our discussion to the regulation of these NPC and kinetochore localizations by mitotic kinase and spindle microtubules.
在后生动物中,动粒在着丝粒染色质上的组装和核孔复合物的解体是必须紧密协调的过程,以确保有丝分裂纺锤体的正确组装和有丝分裂的成功。因此,值得注意的是,这两个大分子组装体共享一组成分。其中一个多方面的成分是 Cenp-F,一种与癌症和发育病理学有关的蛋白质。在细胞周期中,Cenp-F 定位于多个细胞结构中,包括晚 G2/早前期的核膜和有丝分裂过程中的动粒。我们最近描述了 Cenp-F 与 Nup133 相互作用的分子决定因素,Nup133 是核孔的结构组成部分。与另外两项独立研究平行,我们进一步阐明了控制 Cenp-F 动粒募集的机制,该机制主要依赖于其与 Bub1 的相互作用,在急性微管解聚时,Cenp-E 的冗余贡献。在这里,我们综合了当前关于 Cenp-F 在核孔和动粒的双重定位的文献,并将我们的讨论扩展到有丝分裂激酶和纺锤体微管对这些 NPC 和动粒定位的调节。