Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2-mediated mitotic spindle checkpoint
Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2-mediated mitotic spindle checkpoint
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DOI：
10.1101/gad.1677208
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发表时间：
2008-11-01
影响因子：
10.5
通讯作者：
McCormick, Frank
中科院分区：
文献类型：
--
作者：
Lee, Sang Hyun;Sterling, Harry;McCormick, Frank
有丝分裂阻滞缺陷蛋白Mad 1与Mad 2形成复合物，这是对纺锤体组装受到干扰的细胞施加有丝分裂阻滞所必需的。通过亲和纯化的Mad 2相关因子的质谱分析，我们确定了核孔复合物（NPC）的一个组成部分，易位启动子区（Tpr），作为一种新的Mad 2相互作用蛋白。TPR直接与Mad 1和Mad 2结合。HeLa细胞中Tpr的耗尽破坏了Mad 1和Mad 2在间期的NPC定位，并降低了Mad 1结合Mad 2的水平。此外，Tpr的耗竭降低了前中期期间着丝粒处的Mad 1水平，这与Mad 1不能激活Mad 2相关，而Mad 2是抑制APC（Cdc 20）所需的。这些发现揭示了Tpr的重要作用，其中Mad 1-Mad 2蛋白在细胞周期和有丝分裂纺锤体检查点信号传导过程中受到调节。
The mitotic arrest-deficient protein Mad1 forms a complex with Mad2, which is required for imposing mitotic arrest on cells in which the spindle assembly is perturbed. By mass spectrometry of affinity-purified Mad2-associated factors, we identified the translocated promoter region (Tpr), a component of the nuclear pore complex (NPC), as a novel Mad2-interacting protein. Tpr directly binds to Mad1 and Mad2. Depletion of Tpr in HeLa cells disrupts the NPC localization of Mad1 and Mad2 during interphase and decreases the levels of Mad1-bound Mad2. Furthermore, depletion of Tpr decreases the levels of Mad1 at kinetochores during prometaphase, correlating with the inability of Mad1 to activate Mad2, which is required for inhibiting APC(Cdc20). These findings reveal an important role for Tpr in which Mad1-Mad2 proteins are regulated during the cell cycle and mitotic spindle checkpoint signaling.