细胞周期蛋白依赖性激酶 1（Cdk1）对于细胞分裂和抑制 DNA 再复制是必需的，但对于肝脏再生则不是必需的。
Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration.
机构信息
Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (ASTAR), Republic of Singapore 138673.
出版信息
Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3826-31. doi: 10.1073/pnas.1115201109. Epub 2012 Feb 21.
Abstract
Cyclin-dependent kinase 1 (Cdk1) is an archetypical kinase and a central regulator that drives cells through G2 phase and mitosis. Knockouts of Cdk2, Cdk3, Cdk4, or Cdk6 have resulted in viable mice, but the in vivo functions of Cdk1 have not been fully explored in mammals. Here we have generated a conditional-knockout mouse model to study the functions of Cdk1 in vivo. Ablation of Cdk1 leads to arrest of embryonic development around the blastocyst stage. Interestingly, liver-specific deletion of Cdk1 is well tolerated, and liver regeneration after partial hepatectomy is not impaired, indicating that regeneration can be driven by cell growth without cell division. The loss of Cdk1 does not affect S phase progression but results in DNA re-replication because of an increase in Cdk2/cyclin A2 activity. Unlike other Cdks, loss of Cdk1 in the liver confers complete resistance against tumorigenesis induced by activated Ras and silencing of p53.
摘要
周期蛋白依赖性激酶 1（Cdk1）是一种典型的激酶，也是一种核心调节剂，它驱动细胞通过 G2 期和有丝分裂。Cdk2、Cdk3、Cdk4 或 Cdk6 的敲除导致了具有活力的小鼠，但 Cdk1 的体内功能在哺乳动物中尚未得到充分探索。在这里，我们生成了一种条件性敲除小鼠模型来研究 Cdk1 在体内的功能。Cdk1 的缺失导致胚胎发育在囊胚阶段停滞。有趣的是，肝特异性 Cdk1 的缺失可以很好地耐受，肝部分切除后的肝再生不受损害，表明细胞生长而无需细胞分裂即可驱动再生。Cdk1 的缺失不影响 S 期进程，但由于 Cdk2/周期蛋白 A2 活性增加，导致 DNA 再次复制。与其他 Cdks 不同，肝中 Cdk1 的缺失赋予了对激活的 Ras 和 p53 沉默诱导的肿瘤形成的完全抗性。
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