Roles of mob proteins in mitotic exit

通过胞质分裂将一个细胞分离成两个子细胞，必须与将染色体分离成每一个子细胞紧密协调。在具有开放有丝分裂的生物体中，核膜在每次细胞分裂时被分解和重新组装，核膜组装与染色体分离相协调同样重要。在萌芽酵母中，有丝分裂退出网络(MEN)协调胞质分裂和染色体分离。Mob1是人类必需的蛋白质，Mob1的突变体无法退出有丝分裂。MOB相关蛋白的功能尚不清楚，它由所有多细胞生物体的基因组编码，人类至少有六个单独的MOB蛋白基因。我们已经开始对人类的一种Mob蛋白进行鉴定，并发现它在有丝分裂过程中定位于纺锤体极点和纺锤体中间区。根据核膜的不完全组装判断，这种Mob蛋白的耗尽会导致不能完成有丝分裂。此外，一种名为极光B的染色体蛋白的重新定位在Mob耗尽的细胞中发生了改变，就像在酵母Mob1突变体中一样。人类细胞中的Mob缺失的影响类似于酵母中Mob1突变的影响。这一建议旨在进一步表征Mob蛋白在有丝分裂退出中的作用。我们将确定胞质分裂是否需要这种或其他的Mob蛋白。我们将研究当Mob耗尽时，其他染色体或纺锤体蛋白是否会受到影响，以及Mob耗尽是对细胞周期进程的影响，还是直接对核膜组装的影响。我们还将尝试在多细胞生物体中识别与Mob相互作用的蛋白质。预计这些实验将提供关于控制所有生物体细胞分裂的基本信息。

The separation of a cell into two daughter cells by cytokinesis must be tightly coordinated with the separation of the chromosomes into each of the daughters. In organisms with an open mitosis, where the nuclear envelope is disassembled and reassembled each time the cell divides, it is equally important that nuclear envelope assembly is coordinated with chromosome separation. In the budding yeast, Sacchromyces cerevisiae, the mitotic exit network (MEN) coordinates cytokinesis with chromosome segregation. Mob1 is an essential protein in the MEN and mutants in Mob1 fail to exit mitosis. Mob-related proteins, whose functions are unknown, are encoded by the genomes of all multicellular organisms, with humans having at least six separate genes for Mob proteins. We have begun the characterization of one of the human Mob proteins and have found that it is localized to the spindle poles and spindle midzone during mitosis. Depletion of this Mob protein results in a failure to complete mitosis, as judged by the incomplete assembly of the nuclear envelope. Moreover, the relocation of a chromosomal protein called aurora B is altered in Mob depleted cells, as it is in yeast Mob1 mutants. The effects of Mob depletion in human cells are similar to the effects of Mob1 mutations in yeast. This proposal is aimed at further characterizing the role of Mob proteins in mitotic exit. We will determine whether this or other Mob proteins are required for cytokinesis. We will examine whether other chromosomal or spindle proteins are affected when Mob is depleted, and whether the effects of Mob depletion are on a cell cycle progression or directly on nuclear envelope assembly. We will also attempt to identify proteins that interact with Mob in multicellular organisms. It is anticipated that these experiments will provide basic information on the control of cell division in all organisms.