BubR1 is an effector of multiple mitotic kinases that specifies kinetochore: Microtubule attachments and checkpoint
BubR1 is an effector of multiple mitotic kinases that specifies kinetochore: Microtubule attachments and checkpoint
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DOI：
10.4161/cc.8.8.8151
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发表时间：
2009-04-15
期刊：
影响因子：
4.3
通讯作者：
Yen, Timothy J.
中科院分区：
文献类型：
--
作者：
Huang, Haomin;Yen, Timothy J.
BubR1是有丝分裂检查点的关键组成部分，但也被证明在建立着丝点：微管附着物中起重要作用。BubR1在有丝分裂中被过度磷酸化，最近在人类和非洲爪蟾的研究中发现了9个磷酸化位点。据报道，plk1依赖性磷酸化（T792， T1008和S676）刺激BubR1激酶活性，促进着丝点微管附着，监测着丝点张力，以及Mad2检查点蛋白向着丝点募集。与plk1无关的位点（S435、S543、S670和S1043）也被发现，其中一些位点对微管附着的丧失敏感，但对张力不敏感。功能研究表明，S670的磷酸化对纠正异常附着至关重要。一旦端上附着物建立，S670的去磷酸化似乎对产生张力以信号后期开始很重要。这些数据与早期的电镜研究相结合，表明BubR1存在于内外着丝点板，这表明BubR1可能是多种激酶的效应物，在微管附着和检查点功能中发挥作用。
BubR1 is a critical component of the mitotic checkpoint but has also been shown to play an essential role in establishing kinetochore: microtubule attachments. BubR1 is hyperphosphorylated in mitosis and recent studies in human and Xenopus have identified 9 phosphorylation sites. Plk1-dependent phosphorylations (T792, T1008 and S676) were reported to stimulate BubR1 kinase activity, promote kinetochore microtubule attachments, monitor kinetochore tension, as well as the recruitment of Mad2 checkpoint protein to kinetochores. Plk1-independent sites (S435, S543, S670 and S1043) were also identified and some of these were found to be sensitive to the loss of microtubule attachment but not tension. Functional studies showed that phosphorylation of S670 is critical for correcting aberrant attachments. Once end-on attachments are established, dephosphorylation of S670 appeared to be important for generating tension to signal anaphase onset. The collective data when combined with early EM studies that showed BubR1 is present at both the inner and outer kinetochore plates suggest that BubR1 maybe an effector of multiple kinases that specifies its roles in microtubule attachments and checkpoint functions.