Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation

Tong Shin Chang, Woojin Jeong, Soon Young Choi, Shiqin Yu, Sang Won Kang, Sue Goo Rhee

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

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 (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 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 H2O2 might be important for progression of the cell cycle.

Original languageEnglish
Pages (from-to)25370-25376
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number28
DOIs
StatePublished - 12 Jul 2002

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