Roles of mob proteins in mitotic exit

通过胞质分裂将细胞分离成两个子细胞必须与染色体分离成每个子细胞紧密协调。 在具有开放有丝分裂的生物体中，每次细胞分裂时，核膜被拆卸并重新组装，核膜组装与染色体分离协调同样重要。 在芽殖酵母，酿酒酵母，有丝分裂出口网络（MEN）协调胞质分裂与染色体分离。 Mob 1是MEN中的必需蛋白，Mob 1的突变体不能退出有丝分裂。 Mob-related蛋白质，其功能未知，由所有多细胞生物的基因组编码，人类至少有六个独立的Mob蛋白基因。 我们已经开始的人类Mob蛋白的特性之一，并已发现，它是本地化的纺锤体极和纺锤体中间区在有丝分裂。 这种Mob蛋白的缺失导致有丝分裂不能完成，这可以通过核膜的不完全组装来判断。 此外，在Mo B缺失的细胞中，称为极光B的染色体蛋白的重新定位发生了改变，就像在酵母Mob 1突变体中一样。 在人类细胞中Mob缺失的影响与酵母中Mob 1突变的影响相似。 该提议旨在进一步表征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蛋白是否是胞质分裂所必需的。 我们将研究是否其他染色体或纺锤体蛋白质的影响时，Mob耗尽，以及是否Mob耗尽的影响是对细胞周期的进展或直接对核膜组装。 我们还将尝试识别在多细胞生物中与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.