Silencing of human Int-6 impairs mitosis progression and inhibits cyclin B-Cdk1 activation
Silencing of human Int-6 impairs mitosis progression and inhibits cyclin B-Cdk1 activation
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DOI：
10.1038/sj.onc.1208268
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发表时间：
2005-02-10
期刊：
影响因子：
8
通讯作者：
Jalinot, P
中科院分区：
文献类型：
--
作者：
Morris, C;Jalinot, P
Int-6蛋白最初被鉴定为小鼠基因的产物，该基因是小鼠乳腺肿瘤病毒的频繁整合位点。在这里，我们发现通过 RNA 干扰减少 HeLa 细胞中 Int-6 的表达可显着改变有丝分裂进程。观察到纺锤体形成、染色体分离和胞质分裂的缺陷。由于 Cdk1 的抑制性磷酸化状态延长，有丝分裂完成的这些异常与细胞周期蛋白 B Cdk1 激酶活性的抑制相关。与这一观察结果一致，在 Int-6 耗尽的细胞中，负控制 Cdk1 的 Wee1 酪氨酸激酶在 G2 期间失活的效率较低。这些发现支持这样的观点：与 Int-6 改变相关的致癌特性源于染色体不稳定性。
The Int-6 protein has been originally identified as the product of a mouse gene being a frequent integration site of the mouse mammary tumour virus. Here, we show that reducing Int-6 expression by RNA interference in HeLa cells markedly alters mitosis progression. Defects in spindle formation, chromosome segregation and cytokinesis were observed. These abnormalities of mitosis completion are correlated with an inhibition of cyclin B Cdk1 kinase activity, due to a prolonged inhibitory phosphorylated state of Cdk1. In line with this observation, the Wee1 tyrosine kinase that negatively controls Cdk1 was less efficiently inactivated during G2 in Int-6-depleted cells. These findings support the notion that the oncogenic properties associated with alteration of Int-6 originate from chromosomal instability.