Skp2-Cyclin A Interaction Is Necessary for Mitotic Entry and Maintenance of Diploidy.

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.

Citation

Biju Vasavan, Nilanjana Das, Paria Kahnamouei, Chantelle Trombley, Andrew Swan. Skp2-Cyclin A Interaction Is Necessary for Mitotic Entry and Maintenance of Diploidy. Journal of molecular biology. 2024 Apr 15;436(8):168505

Mesh Tags

PMID: 38423454

search → result