Lim et al. show how hydrogen peroxide at the centrosome spurs cells to advance through mitosis.
Cdk1 and regulatory proteins such as cyclin B1, Plk1, and Aurora A cooperate to initiate mitosis. To exit mitosis, cells destroy the regulatory proteins, an effect triggered by the APC/C when it is bound to its coactivator Cdh1. Cdk1 adds phosphates to Cdh1 that prevent it from attaching to the APC/C, but the phosphatase Cdc14B removes them. Cdh1, Cdc14B, and the components of the APC/C are present at the centrosome, but it is unclear how cells rein in Cdc14B activity during early mitosis to prevent premature activation of the APC/C-Cdh1 combo.
Lim et al. discovered that hydrogen peroxide helps control Cdc14B activity. The amount of hydrogen peroxide in a cell starts to rise as it enters G2, but the researchers found that an enzyme called peroxiredoxin I shelters the centrosome. Cells phophorylated and inactivated peroxiredoxin I near the beginning of mitosis, causing a surge in hydrogen peroxide around the centrosome that spurred mitotic progression. Targeting an enzyme that neutralizes hydrogen peroxide to the centrosome delayed cells’ entry into mitosis.
The rise in hydrogen peroxide at the centrosome shut down phosphatases such as Cdc14B, allowing phosphorylation of Cdh1 and inactivation of the APC/C. Later in mitosis, phosphatases PP1 and PP2A stepped in to dephosphorylate and reactivate peroxiredoxin I, cutting hydrogen peroxide levels and allowing the APC/C to begin its work.
Text by Mitch Leslie