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个子细胞紧密协调。在开放有丝分裂的生物体中，核膜每次分裂时都会分解和重组，核膜组装与染色体分离相协调也同样重要。在萌芽酵母中，有丝分裂出口网络(MEN)协调胞质分裂和染色体分离。Mob1是人类必需的蛋白质，Mob1突变体无法退出有丝分裂。Mob相关蛋白由所有多细胞生物的基因组编码，其功能尚不清楚。人类至少有六个不同的Mob蛋白基因。我们已经开始对人类Mob蛋白中的一种进行表征，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蛋白的耗尽导致无法完成有丝分裂，根据核膜的不完全组装来判断。此外，在Mob耗竭的细胞中，一种名为极光B的染色体蛋白的重新定位发生了改变。就像在酵母Mob1突变体中一样。在人类细胞中，Mob耗尽的影响类似于酵母中Mob1突变的影响。这项建议旨在进一步表征Mob蛋白在有丝分裂退出中的作用。我们将确定这种或其他Mob蛋白是否是细胞质分裂所必需的。我们将检查当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的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所有生物中控制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.