Skp2-mediated degradation of p27 regulates progression into mitosis
Skp2-mediated degradation of p27 regulates progression into mitosis
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DOI：
10.1016/s1534-5807(04)00131-5
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发表时间：
2004-05-01
影响因子：
11.8
通讯作者：
Nakayama, KI
中科院分区：
文献类型：
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作者：
Nakayama, K;Nagahama, H;Nakayama, KI
尽管Skp2有；Skp2（-/-）细胞在S-G(2)期表现出p27的积累，并伴有过度复制，被认为在G(1)- s过渡期间介导p27的降解。我们证明Skp2(-/-)p27（-/-）小鼠不表现出过度复制表型，这表明p27的积累是其发育所必需的。Skp2（-/-）小鼠的肝细胞在有丝分裂刺激后进入内复制周期，而Skp2(-/-)p27（-/-）小鼠的这种表型不明显。与野生型细胞相比，Skp2（-/-）细胞中的Cdc2相关激酶活性较低，Cdc2活性的降低足以诱导过度复制。因此，Skp2（-/-）细胞在G(2)期缺乏p27降解可能导致Cdc2活性受到抑制，从而抑制进入M期。这些数据表明，p27蛋白水解对于Cdk2和Cdc2的激活都是必需的，并且Skp2通过介导p27的降解来调节G(2)-M的进展。
Although Skp2 has; been thought to mediate the degradation of p27 at the G(1)-S transition, Skp2(-/-) cells exhibit accumulation of p27 in S-G(2) phase with over-replication. We demonstrate that Skp2(-/-)p27(-/-) mice do not exhibit the overreplication phenotype, suggesting that p27 accumulation is required for its development. Hepatocytes of Skp2(-/-) mice entered the endoduplication cycle after mitogenic stimulation, whereas this phenotype was not apparent in Skp2(-/-)p27(-/-) mice. Cdc2-associated kinase activity was lower in Skp2(-/-) cells than in wild-type cells, and a reduction in Cdc2 activity was sufficient to induce overreplication. The lack of p27 degradation in G(2) phase in Skp2(-/-) cells may thus result in suppression of Cdc2 activity and consequent inhibition of entry into M phase. These data suggest that p27 proteolysis is necessary for the activation of not only Cdk2 but also Cdc2, and that Skp2 contributes to regulation of G(2)-M progression by mediating the degradation of p27.