PP1 – turbocharging mitotic exit

PP1 – turbocharging mitotic exit

The cell cycle is fundamental in biology, as its (mis)regulation is in involved development, ageing, and cancer. In this Molecular Biology of the Cell paper, researchers from Ulrike Gruneberg’s lab in the Dunn school, in collaboration with the Barr lab in the Department of Biochemistry, explore the requirement for the phosphatase PP1 at the metaphase-to-anaphase transition.

Anaphase, the process by which sister chromatids are equally divided between daughter cells during cell division, begins with the degradation of cyclin B which inactivates the mitotic Cdk1-cyclin B kinase. This is facilitated by the anaphase promoting complex (APC/C) together with its essential co-activator CDC20. Cdk1-cyclin B inhibits anaphase onset by phosphorylating CDC20, which prevents its efficient binding to the APC/C. When cyclin B degradation starts, this inhibition is relieved, further driving APC/C activation. The de-phosphorylation of CDC20 which enables this positive feedback loop is therefore a key regulatory step initiating anaphase onset.

In this paper, James Bancroft, James Holder, Zoë Geraghty and their colleagues use a combination of biochemical and live cell imaging approaches in human cells to demonstrate that phosphatase PP1 counters the phosphorylating activity of CDK1 by dephosphorylating CDC20, which results in an active APC/C complex, cyclin B degradation, and appropriate metaphase-to-anaphase transition.

These results add important new insights to our understanding of how PP1 regulates the metaphase-to-anaphase transition in human cells and set the scene for future investigations into further PP1 targets at this stage of the cell cycle.


Alexandra Bisia

Bancroft J, Holder J, Geraghty Z, Alfonso-Pérez T, Murphy D, Barr FA, Gruneberg U.

Mol Biol Cell. mbcE20040252. doi:10.1091/mbc.E20-04-0252