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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。有丝分裂检查点是确保每个新细胞收到每个染色体的一个副本的主要机制。与设立这一检查站有关的一个综合体是Zust White 10/Rough Deal(ZW10/Rod)[1，2]。这两种基因产物最初在果蝇中被鉴定为显示异常有丝分裂进程的突变体[3，4]，随后在果蝇和人类细胞中的研究表明，该复合体与有丝分裂检查点有关。与大多数其他检查点成分不同(参见[5]进行回顾)；然而，完全不清楚这个复合体在检查点信号的产生中起什么作用，而且两者在其主要序列中都没有任何可识别的蛋白质结构域。可能的线索来自已经确定了结合伙伴的研究。P50 Dynamitin是动力蛋白复合体的一个组成部分，是ZW10的结合伙伴；有丝分裂过程中动力蛋白在动点上的定位以及后期染色体的极移依赖于ZW10和Rod[6，7]。然而，动力蛋白抑制对有丝分裂检查点活性的影响与ZW10抑制完全相反：动力蛋白抑制会长期激活检查点，而ZW10抑制会取消检查点。

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.