CENP-E--dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint.
CENP-E--dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint.
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DOI：
10.1083/jcb.201202152
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发表时间：
2012-07-23
期刊：
影响因子：
--
通讯作者：
Mao Y
中科院分区：
文献类型：
--
作者：
Guo Y;Kim C;Ahmad S;Zhang J;Mao Y
CENP-E依赖性BubR 1自身磷酸化响应纺锤体微管捕获的状态调节动粒功能和准确的染色体分离。纺锤体微管在动粒的捕获状态如何转化为有丝分裂检查点信号仍然是未知的。在本文中，我们证明了动粒相关的有丝分裂激酶BubR 1在人类细胞中磷酸化本身，这种自磷酸化依赖于其结合伙伴，动粒电机CENP-E。这种CENP-E依赖的BubR 1在未连接的着丝粒处的自磷酸化对于全强度有丝分裂检查点以防止单个染色体丢失是重要的。用不可磷酸化的BubR 1突变体替换内源性BubR 1，以及耗尽BubR 1激酶激活剂CENP-E，导致中期染色体不对齐和极光B介导的Ndc 80磷酸化在着丝粒处减少。此外，表达拟磷酸化BubR 1突变体大大降低了CENP-E耗尽细胞中极性染色体的发生率。因此，CENP-E依赖的BubR 1自身磷酸化的状态响应于纺锤体微管捕获CENP-E是重要的动粒功能，在实现准确的染色体分离。
The state of CENP-E–dependent BubR1 autophosphorylation in response to spindle microtubule capture regulates kinetochore function and accurate chromosome segregation. How the state of spindle microtubule capture at the kinetochore is translated into mitotic checkpoint signaling remains largely unknown. In this paper, we demonstrate that the kinetochore-associated mitotic kinase BubR1 phosphorylates itself in human cells and that this autophosphorylation is dependent on its binding partner, the kinetochore motor CENP-E. This CENP-E–dependent BubR1 autophosphorylation at unattached kinetochores is important for a full-strength mitotic checkpoint to prevent single chromosome loss. Replacing endogenous BubR1 with a nonphosphorylatable BubR1 mutant, as well as depletion of CENP-E, the BubR1 kinase activator, results in metaphase chromosome misalignment and a decrease of Aurora B–mediated Ndc80 phosphorylation at kinetochores. Furthermore, expressing a phosphomimetic BubR1 mutant substantially reduces the incidence of polar chromosomes in CENP-E–depleted cells. Thus, the state of CENP-E–dependent BubR1 autophosphorylation in response to spindle microtubule capture by CENP-E is important for kinetochore function in achieving accurate chromosome segregation.
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影响因子：
11.8
作者：
Malureanu, Liviu A.;Jeganathan, Karthik B.;Hamada, Masakazu;Wasilewski, Lisa;Davenport, James;van Deursen, Jan M.
通讯作者：
van Deursen, Jan M.
影响因子：
64.5
作者：
Abrieu, A;Kahana, JA;Cleveland, DW
通讯作者：
Cleveland, DW
影响因子：
10.5
作者：
Elowe, Sabine;Huemmer, Stefan;Nigg, Erich A.
通讯作者：
Nigg, Erich A.
DOI：
10.1073/pnas.0401142101
发表时间：
2004-06-08
影响因子：
11.1
作者：
Kops, GJPL;Foltz, DR;Cleveland, DW
通讯作者：
Cleveland, DW
影响因子：
16.8
作者：
Luo, XL;Tang, ZY;Yu, HT
通讯作者：
Yu, HT