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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 有丝分裂检查点是确保每个新细胞接收每个染色体的一个拷贝的主要机制。与此检查点的建立有关的一个复合体是Zeste白色10/Rough Deal（ZW 10/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方法涉及有丝分裂检查点中的复合物。与大多数其他检查点组分不同（参见[5]进行审查）;然而，完全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。可能的线索来自于已经确定了结合伴侣的研究。p50动力蛋白是动力蛋白复合物的一种组分，是ZW 10的结合伴侣;有丝分裂期间动力蛋白定位于动粒，后期期间染色体随后向极移动依赖于ZW 10和杆[6，7]。然而，与ZW 10抑制相比，动力蛋白抑制对有丝分裂检查点活性具有完全相反的作用：动力蛋白抑制长期激活检查点，而ZW 10抑制消除它。

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.