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: Whereas high H2O2 levels induce cell cycle arrest, low H2O2 levels are required for G1–S and G2–M phase transitions (Havens et al., 2006; Yamaura et al., 2009). The molecular mechanisms by which H2O2 modulates cell cycle progression have remained unclear, however. To examine the possible link between the role of H2O2 in cell cycle regulation and PrxI phosphorylation on Thr90, we monitored this latter event during the cell cycle in HeLa cells that had been synchronized at the G1–S border (0 h) with a double thymidine block and then released for various times. Phosphorylated PrxI (pPrxI) appeared slightly earlier than did the mitotic marker phosphorylated histone H3 (pHH3), and it disappeared in parallel with pHH3 (Fig. 1 A). When HeLa or U2OS cells arrested in prometaphase with nocodazole were released from the arrest, pPrxI disappeared rapidly, with the rate of its loss being slightly greater than that for cyclin B1 or pHH3 (Fig. S1 A).
Affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.