Human Cdc25 A inactivation in response to S phase inhibition and its role in preventing premature mitosis
Human Cdc25 A inactivation in response to S phase inhibition and its role in preventing premature mitosis
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人类 Cdc25 A 对 S 期抑制的失活及其在防止过早有丝分裂中的作用
DOI：
10.1093/embo-reports/kvd018
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发表时间：
2000-07-01
期刊：
影响因子：
7.7
通讯作者：
Draetta, GF
中科院分区：
文献类型：
--
作者：
Molinari, M;Mercurio, C;Draetta, GF
Cdc 25 A磷酸酶是细胞周期G（1）-S转换所必需的，在人类癌症中过表达。我们发现它被泛素化并被蛋白酶体迅速降解，并且其水平从G（1）开始增加，直到有丝分裂。通过用DNA合成抑制剂羟基脲处理细胞，Cdc 25 A的丰度迅速降低，并且这伴随着Cdk 2磷酸酪氨酸含量的增加和Cdk 2激酶活性的降低。Cdc 25 A的过度表达改变了细胞在羟基脲存在下停滞的能力，并导致它们经历过早的染色体凝聚。Cdc 25 A过表达可使肿瘤细胞对DNA复制检查点不敏感，从而导致其基因组不稳定性。
The Cdc25 A phosphatase is required for the G(1)-S transition of the cell cycle and is overexpressed in human cancers. We found that it is ubiquitylated and rapidly degraded by the proteasome and that its levels increase from G(1) until mitosis. By treating cells with the DNA synthesis inhibitor hydroxyurea, Cdc25 A rapidly decreased in abundance, and this was accompanied by an increase-in Cdk2 phosphotyrosine content and a decrease in Cdk2 kinase activity. Cdc25 A overexpression altered the ability of cells to arrest in the presence of hydroxyurea, and caused them to undergo premature chromosome condensation. Cdc25 A overexpression could render tumor cells less sensitive to DNA replication checkpoints, thereby contributing to their genomic instability.