Loss of Cul1 results in early embryonic lethality and dysregulation of cyclin E
Loss of Cul1 results in early embryonic lethality and dysregulation of cyclin E
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DOI：
10.1038/13886
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发表时间：
1999-10-01
期刊：
影响因子：
30.8
通讯作者：
Johnson, RS
中科院分区：
文献类型：
--
作者：
Dealy, MJ;Nguyen, KVT;Johnson, RS
细胞周期转换的顺序时间主要由关键细胞周期蛋白的可用性和活性决定(1)。最近在酵母中的研究发现了一类被称为SCF复合体的泛素连接酶(E3酶)，它调节在G1-S相变中促进(2-4)和抑制(4-6)细胞周期进展的蛋白质的丰度。SCF复合体由三个不变的成分组成，Skp1，Cul-1(酵母中的CDC53)和Rbx1，以及一个可变的F-box蛋白，它将特定的细胞蛋白招募到ubquitin途径进行降解(2，3，5，7-13)。为了研究Cul-1在哺乳动物发育和细胞周期调控中的作用，我们培育了cul1基因缺失的小鼠，并分析了空胚胎和杂合子细胞系。我们证明了Cul1是小鼠早期发育所必需的，并且cul1突变体在胚胎发育过程中未能调节G1周期蛋白Cyclin E(由基因编码)的丰度。
The sequential timing of cell-cycle transitions is primarily governed by the availability and activity of key cell-cycle proteins(1). Recent studies in yeast have identified a class of ubiquitin ligases (E3 enzymes) called SCF complexes, which regulate the abundance of proteins that promote(2-4) and inhibit(4-6) cell-cycle progression at the G1-S phase transition. SCF complexes consist of three invariable components, Skp1, Cul-1 (Cdc53 in yeast) and Rbx1, and a variable F-box protein that recruits a specific cellular protein to the ubquitin pathway for degradation(2,3,5,7-13). To study the role of Cul-1 in mammalian development and cell-cycle regulation, we generated mice deficient for Cul1 and analysed null embryos and heterozygous cell lines. We show that Cul1 is required for early mouse development and that Cul1 mutants fail to regulate the abundance of the G1 cyclin, cyclin E (encoded by Gene), during embryogenesis.