Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss.
Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss.
复制标题
共粒相关的蛋白质-E对于哺乳动物有丝分裂检查点至关重要，以防止由于单染色体损失而导致非整倍性。
DOI：
10.1083/jcb.200303167
复制
发表时间：
2003-08-18
影响因子：
7.8
通讯作者：
Cleveland, Don W
中科院分区：
文献类型：
--
作者：
Weaver, Beth A A;Bonday, Zahid Q;Putkey, Frances R;Kops, Geert J P L;Silk, Alain D;Cleveland, Don W
着丝粒相关蛋白E（CENP-E）是一种重要的有丝分裂驱动蛋白，在着丝粒上有效、稳定地捕获微管是必需的。它还直接结合BubR 1，一种与有丝分裂检查点有关的着丝粒相关激酶，有丝分裂检查点是主要的细胞周期控制途径，其中未连接的着丝粒阻止后期开始。在这里，我们表明，耗尽CENP-E的单个未附着动粒无法阻止进入分裂后期，导致体外原代小鼠成纤维细胞25%的分裂和体内95%的再生肝细胞出现非整倍体。在没有CENP-E的情况下，BubR 1的水平降低被募集到着丝粒，BubR 1激酶活性保持在基础水平。CENP-E在体外结合并直接刺激纯化的BubR 1的激酶活性。因此，CENP-E是增强其结合伴侣BubR 1募集到每个未连接的动粒和刺激BubR 1激酶活性所必需的，暗示它是基础有丝分裂检查点信号的重要放大器。
Centromere-associated protein-E (CENP-E) is an essential mitotic kinesin that is required for efficient, stable microtubule capture at kinetochores. It also directly binds to BubR1, a kinetochore-associated kinase implicated in the mitotic checkpoint, the major cell cycle control pathway in which unattached kinetochores prevent anaphase onset. Here, we show that single unattached kinetochores depleted of CENP-E cannot block entry into anaphase, resulting in aneuploidy in 25% of divisions in primary mouse fibroblasts in vitro and in 95% of regenerating hepatocytes in vivo. Without CENP-E, diminished levels of BubR1 are recruited to kinetochores and BubR1 kinase activity remains at basal levels. CENP-E binds to and directly stimulates the kinase activity of purified BubR1 in vitro. Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal.