Roles of mob proteins in mitotic exit

通过细胞质分裂将一个细胞分离成两个子细胞必须与染色体分离成每一个子细胞紧密协调。在开放有丝分裂的生物体中，每次细胞分裂时核膜都被拆卸和重组，核膜的组装与染色体分离的协调同样重要。在出芽酵母，酿酒酵母，有丝分裂出口网络（MEN）协调细胞分裂与染色体分离。Mob1是MEN的一种必需蛋白，而Mob1的突变体不能退出有丝分裂。所有多细胞生物的基因组都对Mob相关蛋白进行编码，其功能尚不清楚，人类至少有6个独立的Mob蛋白基因。我们已经开始表征一种人类Mob蛋白，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。这种Mob蛋白的耗竭会导致有丝分裂失败，这可以通过核包膜的不完全组装来判断。此外，一种叫做极光B的染色体蛋白的重新定位在Mob缺失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Mob基因缺失的影响与酵母中Mob1基因突变的影响相似。这一建议旨在进一步表征暴徒蛋白在有丝分裂退出中的作用。我们将确定细胞分裂是否需要这种或其他Mob蛋白。我们将研究当Mob耗尽时是否会影响其他染色体或纺锤体蛋白，以及Mob耗尽的影响是对细胞周期进程还是直接对核膜组装产生影响。我们也将尝试在多细胞生物中识别与Mob相互作用的蛋白质。预计这些实验将为所有生物细胞分裂的控制提供基本信息。

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.