BubR1 is essential for kinetochore localization of other spindle checkpoint proteins and its phosphorylation requires Mad1.
BubR1 is essential for kinetochore localization of other spindle checkpoint proteins and its phosphorylation requires Mad1.
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DOI：
10.1083/jcb.200204048
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发表时间：
2002-08-05
期刊：
影响因子：
--
通讯作者：
Chen RH
中科院分区：
文献类型：
--
作者：
Chen RH
纺锤体检查点延迟后期开始，直到所有染色体都正确地附着到有丝分裂纺锤体上。在不与纺锤体微管结合或不处于张力下的动粒处产生检查点信号。未连接的动粒与几种检查点蛋白相关，包括BubR1，Bub1，Bub3，Mad1，Mad2和CENP-E。我在此表明，BubR1是重要的纺锤体检查点在非洲爪蟾卵提取物。蛋白质积累并在未连接的动粒处过度磷酸化。BubR1的免疫耗竭大大降低了Bub1、Bub3、Mad1、Mad2和CENP-E的动粒结合。BubR1的缺失也损害了Mad2、Bub3和后期激活剂Cdc20之间的相互作用。这些缺陷被野生型、激酶死亡或缺乏其激酶结构域的截短的BubR1拯救，表明BubR1的激酶活性对于卵提取物中的纺锤体检查点不是必需的。此外，定位和过度磷酸化的BubR1在着丝粒依赖于Bub1和Mad1，但不Mad2。本文表明，BubR1在其他纺锤体检查点蛋白的动粒关联中起着重要作用，Mad1促进BubR1在动粒的过度磷酸化。
The spindle checkpoint delays anaphase onset until all chromosomes have attached properly to the mitotic spindle. Checkpoint signal is generated at kinetochores that are not bound with spindle microtubules or not under tension. Unattached kinetochores associate with several checkpoint proteins, including BubR1, Bub1, Bub3, Mad1, Mad2, and CENP-E. I herein show that BubR1 is important for the spindle checkpoint in Xenopus egg extracts. The protein accumulates and becomes hyperphosphorylated at unattached kinetochores. Immunodepletion of BubR1 greatly reduces kinetochore binding of Bub1, Bub3, Mad1, Mad2, and CENP-E. Loss of BubR1 also impairs the interaction between Mad2, Bub3, and Cdc20, an anaphase activator. These defects are rescued by wild-type, kinase-dead, or a truncated BubR1 that lacks its kinase domain, indicating that the kinase activity of BubR1 is not essential for the spindle checkpoint in egg extracts. Furthermore, localization and hyperphosphorylation of BubR1 at kinetochores are dependent on Bub1 and Mad1, but not Mad2. This paper demonstrates that BubR1 plays an important role in kinetochore association of other spindle checkpoint proteins and that Mad1 facilitates BubR1 hyperphosphorylation at kinetochores.
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影响因子：
64.8
作者：
Cahill, DP;Lengauer, C;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
5.3
作者：
Farr, KA;Hoyt, MA
通讯作者：
Hoyt, MA
影响因子：
5.3
作者：
Millband, DN;Hardwick, KG
通讯作者：
Hardwick, KG
影响因子：
4
作者：
Amon, A
通讯作者：
Amon, A
响应染色体单向化的检查点延迟后期是由未连接的动物学产生的抑制信号介导的。
影响因子：
7.8
作者：
RIEDER, CL;COLE, RW;KHODJAKOV, A;SLUDER, G
通讯作者：
SLUDER, G