TRIP13PCH-2 promotes Mad2 localization to unattached kinetochores in the spindle checkpoint response.
TRIP13PCH-2 promotes Mad2 localization to unattached kinetochores in the spindle checkpoint response.
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DOI：
10.1083/jcb.201505114
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发表时间：
2015-11-09
期刊：
影响因子：
--
通讯作者：
Bhalla N
中科院分区：
文献类型：
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作者：
Nelson CR;Hwang T;Chen PH;Bhalla N
保守的ATP酶TRIP 13 PCH-2分解含有Mad 2的复合物的能力对于通过促进Mad 2到未连接的动粒的稳健定位来促进纺锤体检查点响应是至关重要的。纺锤体检查点在细胞分裂过程中起作用，以防止非整倍体，这是癌症的标志。在检查点激活期间，Mad 1将Mad 2招募到动粒中以产生延迟后期开始的信号。然而，是否有其他因素有助于Mad 2的动粒定位仍不清楚。在这里，我们报告说，保守的AAA+ ATP酶TRIP 13 PCH-2定位于未连接的动粒，并需要纺锤体检查点激活秀丽隐杆线虫。pch-2突变体有效地将Mad 1定位于独立的动粒，但Mad 2的募集显著减少。此外，我们还证明了C. Mad 2抑制剂p31（comet）CMT-1的秀丽线虫直向同源物与TRIP 13 PCH-2相互作用，并且是其定位于未连接的动粒所必需的。这些因素也在遗传上相互作用，因为p31（彗星）CMT-1的缺失部分抑制了Mad 2定位和纺锤体检查点信号传导中对TRIP 13 PCH-2的需求。这些数据支持一种模型，其中TRIP 13 PCH-2分解p31（彗星）/Mad 2复合物的能力，其在检查点沉默的背景下已经被很好地表征，对于纺锤体检查点激活也是至关重要的。
The ability of the conserved ATPase TRIP13PCH-2 to disassemble a Mad2-containing complex is critical to promote the spindle checkpoint response by contributing to the robust localization of Mad2 to unattached kinetochores. The spindle checkpoint acts during cell division to prevent aneuploidy, a hallmark of cancer. During checkpoint activation, Mad1 recruits Mad2 to kinetochores to generate a signal that delays anaphase onset. Yet, whether additional factors contribute to Mad2’s kinetochore localization remains unclear. Here, we report that the conserved AAA+ ATPase TRIP13PCH-2 localizes to unattached kinetochores and is required for spindle checkpoint activation in Caenorhabditis elegans. pch-2 mutants effectively localized Mad1 to unattached kinetochores, but Mad2 recruitment was significantly reduced. Furthermore, we show that the C. elegans orthologue of the Mad2 inhibitor p31(comet)CMT-1 interacts with TRIP13PCH-2 and is required for its localization to unattached kinetochores. These factors also genetically interact, as loss of p31(comet)CMT-1 partially suppressed the requirement for TRIP13PCH-2 in Mad2 localization and spindle checkpoint signaling. These data support a model in which the ability of TRIP13PCH-2 to disassemble a p31(comet)/Mad2 complex, which has been well characterized in the context of checkpoint silencing, is also critical for spindle checkpoint activation.