Wojcik E J, Glover D M, Hays T S
Department of Biology, Virginia Tech University, Blacksburg, Virginia, 24061, USA.
Curr Biol. 2000 Sep 21;10(18):1131-4. doi: 10.1016/s0960-9822(00)00703-x.
The duplication of the centrosome is a key event in the cell-division cycle. Although defects in centrosome duplication are thought to contribute to genomic instability [1-3] and are a hallmark of certain transformed cells and human cancer [4-6], the mechanism responsible for centrosome duplication is not understood. Recent experiments have established that centrosome duplication requires the activity of cyclin-dependent kinase 2 (Cdk2) and cyclins E and A [7-9]. The stability of cyclin E is regulated by the ubiquitin ligase SCF, which is a protein complex composed of Skp1, Cdc53 (Cullin) and F-box proteins [10-12]. The Skp1 and Cullin components have been detected on mammalian centrosomes, and shown to be essential for centrosome duplication and separation in Xenopus [13]. Here, we report that Slimb, an F-box protein that targets proteins to the SCFcomplex [14,15], plays a role in limiting centrosome replication. We found that, in the fruit fly Drosophila, the hypomorphic mutation slimb(crd) causes the appearance of additional centrosomes and mitotic defects in mutant larval neuroblasts.
中心体的复制是细胞分裂周期中的一个关键事件。尽管中心体复制缺陷被认为会导致基因组不稳定[1-3]，并且是某些转化细胞和人类癌症的一个标志[4-6]，但负责中心体复制的机制仍不清楚。最近的实验已经证实，中心体复制需要细胞周期蛋白依赖性激酶2（Cdk2）以及细胞周期蛋白E和A的活性[7-9]。细胞周期蛋白E的稳定性由泛素连接酶SCF调节，SCF是一种由Skp1、Cdc53（Cullin）和F-box蛋白组成的蛋白质复合物[10-12]。在哺乳动物中心体上已经检测到Skp1和Cullin成分，并且在非洲爪蟾中显示它们对于中心体的复制和分离至关重要[13]。在此，我们报告Slimb，一种将蛋白质靶向SCF复合物的F-box蛋白[14,15]，在限制中心体复制中发挥作用。我们发现，在果蝇中，亚效突变体slimb(crd)会导致突变幼虫神经母细胞中出现额外的中心体和有丝分裂缺陷。
