Control of the pericentrosomal H2O2 level by peroxiredoxin I is critical for mitotic progression.
Bottom Line: The intracellular concentration of H2O2 increases as the cell cycle progresses.Whereas the centrosome is shielded from H2O2 through its association with the H2O2-eliminating enzyme peroxiredoxin I (PrxI) during interphase, the centrosome-associated PrxI is selectively inactivated through phosphorylation by Cdk1 during early mitosis, thereby exposing the centrosome to H2O2 and facilitating inactivation of centrosome-bound phosphatases.Dephosphorylation of PrxI by okadaic acid-sensitive phosphatases during late mitosis again shields the centrosome from H2O2 and thereby allows the reactivation of Cdk1-opposing phosphatases at the organelle.
Affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.Show MeSH
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Mentions: A series of events that are proposed to occur at the centrosome in connection to H2O2 is shown schematically in Fig. 5, beginning with PrxI phosphorylation. Whereas the intracellular concentration of H2O2 increases as the cell cycle progresses to G2 phase, the centrosome is shielded from the high tide of H2O2 by the peroxidase activity of PrxI associated with the organelle. At the onset of mitosis, Cdk1–cyclin B phosphorylates PrxI, which results in exposure of the centrosome to H2O2 and consequent inactivation of Cdk1-opposing phosphatases represented by Cdc14B. Among the many Cdk1-phosphorylated proteins in mammalian cells, at least pCdh1 appears to be a substrate of Cdc14B in vitro and in vivo (Bassermann et al., 2008; Schindler and Schultz, 2009; Mocciaro and Schiebel, 2010). In late mitosis, PrxI is dephosphorylated, and the centrosome is consequently again shielded from H2O2, allowing sequential reactivation of phosphatases, dephosphorylation of Cdh1, and activation of APC/C-Cdh1. This newly discovered circuit provides a means to integrate input from diverse H2O2-generating cellular processes. The presence of PrxI at the centrosome might also serve as a safeguard to prevent unscheduled mitotic entry as a result of an accidental increase in H2O2 abundance.
Affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.