Skp2 是 SCFSkp2 泛素连接酶的底物识别组件，与许多关键细胞周期调节因子的靶向破坏和 S 期的促进有关。其关键靶标之一是细胞周期蛋白依赖性激酶 (Cdk) 抑制剂 p27，事实上，许多癌症中 Skp2 的过度表达与 p27 的过早降解直接相关。 Skp2 最初被鉴定为一种在转化细胞中与细胞周期蛋白 A 相互作用的蛋白质，但其在该复合物中的作用仍不清楚。在本文中，我们证明 Skp2 与果蝇中的 Cyclin A 相互作用，并且是维持 Cyclin A 水平并允许有丝分裂进入所必需的。 Skp2 突变细胞中有丝分裂进入失败会导致多倍体。如果这些细胞再次进入有丝分裂，它们就无法正确分离染色体，导致检查点依赖性细胞周期停滞或凋亡。因此，Skp2 是有丝分裂以及维持二倍体和基因组稳定性所必需的。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Skp2, the substrate recognition component of the SCFSkp2 ubiquitin ligase, has been implicated in the targeted destruction of a number of key cell cycle regulators and the promotion of S-phase. One of its critical targets is the Cyclin dependent kinase (Cdk) inhibitor p27, and indeed the overexpression of Skp2 in a number of cancers is directly correlated with the premature degradation of p27. Skp2 was first identified as a protein that interacts with Cyclin A in transformed cells, but its role in this complex has remained unclear. In this paper, we demonstrate that Skp2 interacts with Cyclin A in Drosophila and is required to maintain Cyclin A levels and permit mitotic entry. Failure of mitotic entry in Skp2 mutant cells results in polyploidy. If these cells enter mitosis again they are unable to properly segregate their chromosomes, leading to checkpoint dependent cell cycle arrest or apoptosis. Thus, Skp2 is required for mitosis and for maintaining diploidy and genome stability.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.