Drosophila skpA, a component of SCF ubiquitin ligases, regulates centrosome duplication independently of cyclin E accumulation
Drosophila skpA, a component of SCF ubiquitin ligases, regulates centrosome duplication independently of cyclin E accumulation
复制标题
DOI：
10.1242/jcs.00463
复制
发表时间：
2003-06-01
影响因子：
4
通讯作者：
Murphy, TD
中科院分区：
文献类型：
--
作者：
Murphy, TD
中心体复制必须与主细胞周期相连，以确保每个细胞在有丝分裂开始时正好有两个中心体。多余的中心体在癌细胞中很常见，可能与肿瘤的发生有关。果蝇skpA是干细胞因子泛素连接酶的一个组成部分，调节细胞和中心体周期之间的联系。致死性skpA缺失突变体表现出显著的中心体过度复制和染色质凝聚、细胞周期进展和内复制的额外缺陷。令人惊讶的是，许多突变细胞能够在额外功能中心体的存在下组织假双极纺锤体并执行正常的后期。SkpA突变细胞在S和G2期积累的细胞周期蛋白E水平高于野生型细胞，提示CDK2/Cyclin E活性升高可能是SkpA(-)细胞中心体增多的原因。然而，在skpA(-)；cycE(-)突变动物中仍然存在中心体过度复制，这表明高水平的Cyclin E不是中心体过度复制所必需的。这些数据表明，更多的SCF靶点调节中心体复制途径。
Centrosome duplication must be coupled to the main cell cycle to ensure that each cell has precisely two centrosomes at the onset of mitosis. Supernumerary centrosomes are commonly observed in cancer cells, and may contribute to tumorigenesis. Drosophila skpA, a component of SCF ubiquitin ligases, regulates the link between the cell and centrosome cycles. Lethal skpA null mutants exhibit dramatic centrosome overduplication and additional defects in chromatin condensation, cell cycle progression and endoreduplication. Surprisingly, many mutant cells are able to organize pseudo-bipolar spindles and execute a normal anaphase in the presence of extra functional centrosomes. SkpA mutant cells accumulate higher levels of cyclin E than wildtype cells during S and G2, suggesting that elevated cdk2/cyclin E activity may account for the supernumerary centrosomes in skpA(-) cells. However, centrosome overduplication still occurs in skpA(-); cycE(-) mutant animals, demonstrating that high cyclin E levels are not necessary for centrosome overduplication. These data suggest that additional SCF targets regulate the centrosome duplication pathway.