Regulation of Peroxiredoxin I Activity by Cdc2-mediated Phosphorylation

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 (Thr90-Pro-Lys-Lys) for phosphorylation by cyclin-dependen...

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Published in:The Journal of biological chemistry 2002-07, Vol.277 (28), p.25370-25376
Main Authors: Chang, Tong-Shin, Jeong, Woojin, Choi, Soon Young, Yu, Shiqin, Kang, Sang Won, Rhee, Sue Goo
Format: Article
Language:English
Subjects:
Amino Acid Sequence
CDC2 Protein Kinase - metabolism
Cell Cycle
HeLa Cells
Humans
Peroxidases - chemistry
Peroxidases - metabolism
Peroxiredoxins
Phosphorylation
Threonine - metabolism
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Summary: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 (Thr90-Pro-Lys-Lys) for phosphorylation by cyclin-dependent kinases (CDKs). This protein has now been shown to be phosphorylated specifically on Thr90 by several CDKs, including Cdc2, in vitro. Phosphorylation of Prx I on Thr90 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 Thr90. 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 Thr90 both in vitroand 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 H2O2 might be important for progression of the cell cycle.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M110432200