Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints
Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints
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DOI：
10.1073/pnas.081076898
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发表时间：
2001-04-10
影响因子：
11.1
通讯作者：
Margolis, RL
中科院分区：
文献类型：
--
作者：
Skoufias, DA;Andreassen, PR;Margolis, RL
中期检查点控制有丝分裂过程中染色体排列的有义异常，并防止进展到后期，直到达到正确的排列。许多蛋白质，包括mad 2，bub 1和bubR 1，都与哺乳动物细胞中的中期检查点控制有关。中期检查点已被证明，在各种系统中，读取纺锤体张力或微管附着在动粒的损失。典型地，HeLa细胞响应于低水平的微管抑制剂而停滞在中期，留下完整的纺锤体和中期板。在这里，我们表明，纳摩尔长春碱诱导的逮捕与在动粒的张力损失，并在响应的检查点蛋白bub 1和bubR 1被招募到动粒，但mad 2不是，mad 2仍然有能力响应，并在较高的药物剂量，破坏纺锤体与动粒协会招募。此外，尽管mad 2与cdc 20形成复合物，但它不与bub 1或bubR 1缔合。我们的结论是，哺乳动物bub 1/bubR 1和mad 2作为不同的传感张力和附件，分别途径的元素。
Metaphase checkpoint controls sense abnormalities of chromosome alignment during mitosis and prevent progression to anaphase until proper alignment has been attained. A number of proteins, including mad2, bub1, and bubR1, have been implicated in the metaphase checkpoint control in mammalian cells. Metaphase checkpoints have been shown, in various systems, to read loss of either spindle tension or microtubule attachment at the kinetochore. Characteristically, HeLa cells arrest in metaphase in response to low levels of microtubule inhibitors that leave an intact spindle and a metaphase plate. Here we show that the arrest induced by nanomolar vinblastine correlates with loss of tension at the kinetochore, and that in response the checkpoint proteins bub1 and bubR1 are recruited to the kinetochore but mad2 is not, mad2 remains competent to respond and is recruited at higher drug doses that disrupt spindle association with the kinetochores. Further, although mad2 forms a complex with cdc20, it does not associate with bub1 or bubR1. We conclude that mammalian bub1/bubR1 and mad2 operate as elements of distinct pathways sensing tension and attachment, respectively.