Roles of mob proteins in mitotic exit

mob蛋白在有丝分裂退出中的作用

• 批准号: 123797-2007
• 负责人: Lohka, ManfredJuergen
• 金额: $ 1.46万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=365681
• 关键词: Roles; mob; proteins; mitotic; exit

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.

通过胞质分裂将一个细胞分成两个子细胞必须与将染色体分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都会分解和重新组装，因此核膜组装与染色体分离相协调同样重要。  在芽殖酵母（酿酒酵母）中，有丝分裂出口网络（MEN）协调胞质分裂和染色体分离。  Mob1 是 MEN 中的必需蛋白，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，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。  我们已经开始对一种人类 Mob 蛋白进行表征，并发现它在有丝分裂期间定位于纺锤体极和纺锤体中区。  根据核膜组装不完整的情况判断，这种 Mob 蛋白的耗尽会导致有丝分裂无法完成。  此外，一种称为 aurora 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。  Mob 缺失对人类细胞的影响与 Mob1 突变对酵母的影响相似。  该提案旨在进一步表征 Mob 蛋白在有丝分裂退出中的作用。  我们将确定该 Mob 蛋白或其他 Mob 蛋白是否是胞质分裂所必需的。  我们将检查 Mob 耗尽时其他染色体或纺锤体蛋白是否受到影响，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。   我们还将尝试鉴定与多细胞生物体中的 Mob 相互作用的蛋白质。  预计这些实验将提供有关所有生物体细胞分裂控制的基本信息。