A complex degradation signal in Cyclin A required for G1 arrest, and a C-terminal region for mitosis
A complex degradation signal in Cyclin A required for G1 arrest, and a C-terminal region for mitosis
复制标题
DOI：
10.1093/emboj/20.10.2376
复制
发表时间：
2001-05-15
期刊：
影响因子：
11.4
通讯作者：
Lehner, CF
中科院分区：
文献类型：
--
作者：
Jacobs, HW;Keidel, E;Lehner, CF
破坏盒（D-box）共有序列被定义为在有丝分裂过程中介导B型细胞周期蛋白的多聚泛素化和蛋白水解的基序。我们在这里证明与D-box相似的区域不是果蝇细胞周期蛋白A有丝分裂降解所必需的。在这种细胞周期蛋白中存在一种复杂的N-末端降解信号，而不是简单的D-盒。削弱或消除有丝分裂细胞周期蛋白A破坏的突变延迟了中期的进展，但只有在过表达时，这些突变才能阻止表皮细胞进入胚胎发生的第一个G（1）期，并导致一个完整的额外分裂周期，而不是及时的细胞增殖停滞，因此，有丝分裂后残留的细胞周期蛋白A活性具有S期促进活性。原则上，S期缺陷也可以解释为什么表皮细胞不能进入有丝分裂16在突变体缺乏合子细胞周期蛋白A功能。然而，我们证明了这种有丝分裂的失败不仅仅是由DNA复制或损伤检查点引起的。进入有丝分裂需要细胞周期蛋白A的功能，不依赖于N-末端区域的存在。
The destruction box (D-box) consensus sequence has been defined as a motif mediating polyubiquitylation and proteolysis of B-type cyclins during mitosis, We show here that the regions with similarity to D-boxes are not required for mitotic degradation of Drosophila Cyclin A. Instead of a simple D-box, a complex N-terminal degradation signal is present in this cyclin, Mutations that impair or abolish mitotic Cyclin A destruction delay progression through metaphase, but only when overexpressed, Moreover, these mutations prevent epidermal cells from entering the first G(1) phase of embryogenesis and lead to a complete extra division cycle instead of a timely cell proliferation arrest, Residual Cyclin A activity after mitosis, therefore, has S phase-promoting activity. In principle, an S phase defect could also explain why epidermal cells fail to enter mitosis 16 in mutants lacking zygotic Cyclin A function. However, we demonstrate that this failure of mitosis is not caused simply by DNA replication or damage checkpoints. Entry into mitosis requires a function of Cyclin A that does not depend on the presence of the N-terminal region.