The regulatory architecture of mitotic entry

Abstract

The timing of mitosis is tightly regulated and is essential for proper development. In this review we investigate how the timing of mitosis is regulated and how this can be altered during development or after development. The main regulator of mitosis is CycB-Cdk1. High CycB Cdk1 activity triggers entry into mitosis. CycB-Cdk1 is surrounded by several layers of regulation. In the inner feedback loop inhibitory phosphorylations are placed and removed. The inner feedback loop is surrounded by the outer feedback loop, whose players regulate the players of the inner feedback loop. To address the question of how the timing and progression through mitosis can be altered, we will look at several examples of this. In several of these examples mitotic timing is altered by changing expression levels of Cdc25, a player of the inner feedback loop. Overexpression of Cdc25 is often seen in cancers and might be a great target for cancer therapies.