title: Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation.
abstract: Hydrogen peroxide is implicated as an intracellular messenger in various cellular responses such as proliferation and differentiation. Peroxiredoxin (Prx) I is a member of the peroxiredoxin family of peroxidases and contains a consensus site (Thr(90)-Pro-Lys-Lys) for phosphorylation by cyclin-dependent kinases (CDKs). This protein has now been shown to be phosphorylated specifically on Thr(90) by several CDKs, including Cdc2, in vitro. Phosphorylation of Prx I on Thr(90) reduced the peroxidase activity of this protein by 80%. The phosphorylation of Prx I in HeLa cells was monitored with the use of antibodies specific for Prx I phosphorylated on Thr(90). Immunoblot analysis with these antibodies of HeLa cells arrested at various stages of the cell cycle revealed that Prx I phosphorylation occurs in parallel with the activation of Cdc2; Prx I phosphorylation was thus marked during mitosis but virtually undetectable during interphase. Furthermore, when Cdc2 expression was reduced by RNA interference with cognate small interfering RNAs, Prx I phosphorylation was not observed in the cells synchronized in mitotic phase. The cytosolic location of Prx I likely prevents its interaction with activated CDKs until after the breakdown of the nuclear envelope during mitosis, when Cdc2 is the CDK that is most active. Phosphorylation of Prx I on Thr(90) both in vitro and in vivo was blocked by roscovitine, an inhibitor of CDKs. These results suggest that Cdc2-mediated phosphorylation and inactivation of Prx I and the resulting intracellular accumulation of H(2)O(2) might be important for progression of the cell cycle.
authors: Laboratory of Cell Signaling, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Tong-Shin
authors: TS
authors: Chang
authors: Woojin
authors: W
authors: Jeong
authors: Soon Young
authors: SY
authors: Choi
authors: Shiqin
authors: S
authors: Yu
authors: Sang Won
authors: SW
authors: Kang
authors: Sue Goo
authors: SG
authors: Rhee
mesh_terms: D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D006367:HeLa Cells; D006801:Humans; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D054464:Peroxiredoxins; D010766:Phosphorylation; D013912:Threonine / Q000378:metabolism
chemical_list: D013912:Threonine; D010544:Peroxidases; D054464:Peroxiredoxins; D016203:CDC2 Protein Kinase