人类Cdc25 A对S期抑制的反应失活及其在防止有丝分裂过早发生中的作用。
Human Cdc25 A inactivation in response to S phase inhibition and its role in preventing premature mitosis.
作者信息
Molinari M, Mercurio C, Dominguez J, Goubin F, Draetta G F
机构信息
European Institute of Oncology, Milan, Italy.
出版信息
EMBO Rep. 2000 Jul;1(1):71-9. doi: 10.1093/embo-reports/kvd018.
Abstract
The Cdc25 A phosphatase is required for the G1-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 G1 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.
摘要
细胞周期蛋白Cdc25 A磷酸酶是细胞周期从G1期向S期转变所必需的，且在人类癌症中过表达。我们发现它会被蛋白酶体泛素化并迅速降解，其水平从G1期到有丝分裂期不断升高。用DNA合成抑制剂羟基脲处理细胞后，Cdc25 A的丰度迅速下降，同时伴随着Cdk2磷酸酪氨酸含量的增加和Cdk2激酶活性的降低。Cdc25 A的过表达改变了细胞在羟基脲存在下停滞的能力，并导致它们过早发生染色体浓缩。Cdc25 A的过表达会使肿瘤细胞对DNA复制检查点的敏感性降低，从而导致其基因组不稳定。
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