Yin6, a fission yeast Int6 homolog, complexes with Moe1 and plays a role in chromosome segregation
Yin6, a fission yeast Int6 homolog, complexes with Moe1 and plays a role in chromosome segregation
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DOI：
10.1073/pnas.97.26.14370
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发表时间：
2000-12-19
影响因子：
11.1
通讯作者：
Chang, EC
中科院分区：
文献类型：
--
作者：
Yen, HCS;Chang, EC
INT6基因与人类乳腺癌的形成有关，但其功能尚不清楚。我们通过与Ras通路中的保守蛋白Moe1结合，从裂变酵母中分离出一个Int6同源物Yin6。Yin6和Moe1聚集在同一个蛋白复合体上，促进微管不稳定/解体。Yin6和Moe1协同作用：当其中一种蛋白缺失时，另一种蛋白定位错误，蛋白水平降低。此外，尽管全长的人Int6挽救了yin6-null （yin6 Delta）突变细胞的表型并结合了人Moe1，但在肿瘤中发现的截断的Int6蛋白却没有。重要的是，yin6 Delta单独损害染色体分离较弱，但yin6 Delta与ras1 Delta一起导致严重的染色体错分离。这些数据支持一个模型，即人类INT6突变单独或与其他突变（如RAS突变）一起可能通过改变基因组稳定性来促进肿瘤发生。
The INT6 gene has been implicated in human breast cancer formation, but its function is unknown. We isolated an Int6 homolog from fission yeast, Yin6 by its binding to a conserved protein in the Ras pathway, Moe1. Yin6 and Moe1 converge on the same protein complex to promote microtubule instability/disassembly. Yin6 and Moe1 interact cooperatively: when either protein is absent, the other becomes mislocalized with decreased protein levels. Furthermore, whereas full-length human Int6 rescues the phenotypes of the yin6-null (yin6 Delta) mutant cells and binds human Moe1, truncated Int6 proteins found in tumors do not Importantly, yin6 Delta alone impairs chromosome segregation weakly, but yin6 Delta together with ras1 Delta causes severe chromosome missegregation. These data support a model in which INT6 mutations in humans either alone or together with additional mutations, such as a RAS mutation, may contribute to tumorigenesis by altering genome stability.