title: Control of the pericentrosomal H2O2 level by peroxiredoxin I is critical for mitotic progression.
abstract: Proteins associated with the centrosome play key roles in mitotic progression in mammalian cells. The activity of Cdk1-opposing phosphatases at the centrosome must be inhibited during early mitosis to prevent premature dephosphorylation of Cdh1-an activator of the ubiquitin ligase anaphase-promoting complex/cyclosome-and the consequent premature degradation of mitotic activators. In this paper, we show that reversible oxidative inactivation of centrosome-bound protein phosphatases such as Cdc14B by H2O2 is likely responsible for this inhibition. 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.
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Lim
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892.
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Woo
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea dkang@ewha.ac.kr rheesg@yuhs.ac.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Kang
authors.affiliation: Yonsei Biomedical Research Institute, Yonsei University, Seoul 120-749, South Korea dkang@ewha.ac.kr rheesg@yuhs.ac.
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D018385:Centrosome / Q000201:enzymology*; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D006861:Hydrogen Peroxide; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D002374:Catalase