A role for the Adenomatous Polyposis Coli protein in chromosome segregation
A role for the Adenomatous Polyposis Coli protein in chromosome segregation
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DOI：
10.1038/35070123
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发表时间：
2001-04-01
影响因子：
21.3
通讯作者：
Näthke, IS
中科院分区：
文献类型：
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作者：
Kaplan, KB;Burds, AA;Näthke, IS
腺瘤性息肉病结肠(APC)基因突变与家族性结肠癌有关，也发生在散发性结肠癌的早期阶段(1)。APC在Wnt信号通路中发挥作用，调节β-连环蛋白的降解(参考文献1-3)。APC还与体内和体外的微管结合并稳定(4)，定位于间期细胞质膜附近的微管末端的簇(5，6)，是细胞骨架功能的重要调节因子(7，8)。在这里，我们表明携带截短的APC基因(Min)(9)的细胞在染色体分离方面是有缺陷的。此外，在有丝分裂过程中，APC定位于嵌入动粒的微管末端，并与检查点蛋白Bub1和Bub3形成复合体。在体外，APC是Pub激酶的高亲和力底物。我们的数据与APC在动粒-微管连接中的作用是一致的，并表明APC中消除微管结合的截断可能有助于癌细胞中的染色体不稳定(10)。
Mutations in the Adenomatous Polyposis Coli (APC) gene are responsible for familial colon cancer and also occur in the early stages of sporadic colon cancer(1). APC functions in the Wnt signalling pathway to regulate the degradation of beta -catenin (reviewed in refs 1-3). APC also binds to and stabilizes microtubules in viva and in vitro(4), localizes to clusters at the ends of microtubules near the plasma membrane of interphase cells(5,6), and is an important regulator of cytoskeletal function(7,8). Here we show that cells carrying a truncated APC gene (Min)(9) are defective in chromosome segregation. Moreover during mitosis, APC localizes to the ends of microtubules embedded in kinetochores and forms a complex with the checkpoint proteins Bub1 and Bub3, In vitro, APC is a high-affinity substrate for Pub kinases. Our data are consistent with a role for APC in kinetochore-microtubule attachment and suggest that truncations in APC that eliminate microtubule binding may contribute to chromosomal instability in cancer cells(10).