Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery.
Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery.
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DOI:
10.1083/jcb.200606005
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发表时间:
2006-12-04
期刊:
影响因子:
--
通讯作者:
Heintz NH
中科院分区:
文献类型:
--
作者:
Phalen TJ;Weirather K;Deming PB;Anathy V;Howe AK;van der Vliet A;Jönsson TJ;Poole LB;Heintz NH
Inactivation of eukaryotic 2-Cys peroxiredoxins (Prxs) by hyperoxidation has been proposed to promote accumulation of hydrogen peroxide (H2O2) for redox-dependent signaling events. We examined the oxidation and oligomeric states of PrxI and -II in epithelial cells during mitogenic signaling and in response to fluxes of H2O2. During normal mitogenic signaling, hyperoxidation of PrxI and -II was not detected. In contrast, H2O2-dependent cell cycle arrest was correlated with hyperoxidation of PrxII, which resulted in quantitative recruitment of ∼66- and ∼140-kD PrxII complexes into large filamentous oligomers. Expression of cyclin D1 and cell proliferation did not resume until PrxII-SO2H was reduced and native PrxII complexes were regenerated. Ectopic expression of PrxI or -II increased Prx-SO2H levels in response to oxidant exposure and failed to protect cells from arrest. We propose a model in which Prxs function as peroxide dosimeters in subcellular processes that involve redox cycling, with hyperoxidation controlling structural transitions that alert cells of perturbations in peroxide homeostasis.
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