IDENTIFYING THE ROLE OF THE ZW10/ROD COMPLEX IN MITOTIC CHECKPOINT SIGNALING

确定 ZW10/ROD 复合物在有丝分裂检查点信号传导中的作用

• 批准号: 7957741
• 负责人: GEERT KOPS
• 金额: $ 0.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957741
• 关键词: Anaphase; Binding; Biology; Cells; Chromosomes; Complex; Computer Retrieval of Information on Scientific Projects Database; DCTN2 gene; Dynein ATPase; Ensure; Funding; Fungal Genome; Generations; Grant; Human; Institution; Kinetochores; Mitosis; Mitotic; Mitotic Checkpoint; Play; Proteins; Research; Research Personnel; Resources; Role; Signal Transduction; Source; TNFRSF5 gene; Tertiary Protein Structure; United States National Institutes of Health; chromosome movement; dynactin; fly; mutant; retinal rods

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The mitotic checkpoint is the primary mechanism for ensuring that each new cell receives one copy of every chromosome. One complex implicated in the establishment of this checkpoint is Zeste White 10/Rough Deal (ZW10/Rod) [1,2]. Both gene products were originally identified in flies as mutants that displayed aberrant mitotic progression [3,4], and subsequent approaches in flies and human cells implicated the complex in the mitotic checkpoint. Unlike most of the other checkpoint components (see [5] for review); however, it is entirely unclear what role this complex plays in the generation of the checkpoint signal, and neither has any recognizable protein domains in their primary seqeunce. Possible clues come from studies that have identified binding partners. p50 dynamitin, a component of the dynactin complex, is a binding partner of ZW10; the localization of dynein to the kinetochores during mitoses and the subsequent poleward movement of the chromosomes during anaphase are dependent on ZW10 and Rod [6,7]. However, dynein inhibition has the exact opposite effect on mitotic checkpoint activity compared to ZW10 inhibition: dynein inhibition chronically activates the checkpoint, whereas ZW10 inhibition abrogates it.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 有丝分裂检查点是确保每个新细胞都会收到每个染色体的一个副本的主要机制。建立该检查点的一个复合物是Zeste White 10/Rough Deal（ZW10/ROD）[1,2]。两种基因产物最初都在蝇中鉴定为表现出异常有丝分裂进展的突变体[3,4]，随后的苍蝇和人类细胞的方法在有丝分裂检查点中涉及该复合物。与大多数其他检查点组件不同（有关审查，请参见[5]）；但是，完全尚不清楚该复合物在检查点信号的产生中起什么作用，并且在其主要seqeunce中都没有任何可识别的蛋白质结构域。可能的线索来自确定约束伙伴的研究。 p50元素是Dynactin复合物的组成部分，是ZW10的结合伴侣。在后期期间，动力蛋白在有丝分裂过程中的定位以及染色体随后的极向运动取决于ZW10和ROD [6,7]。然而，与ZW10抑制相比，动力蛋白抑制对有丝分裂检查点的活性具有完全相反的作用：Dynein抑制作用长期激活检查点，而ZW10抑制作用消除了它。