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:
The Journal of cell biology
影响因子:
--
通讯作者:
Heintz NH
Heintz NH
中科院分区:
其他
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

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真核生物2-Cys过氧化物酶(Prxs)的过氧化作用被认为是促进过氧化氢(H2 O2)积累的氧化还原依赖性信号事件。我们研究了氧化和低聚状态的PrxI和-II在上皮细胞中的有丝分裂信号和响应流量的H2 O2。在正常的促有丝分裂信号,过氧化的PrxI和-II没有检测到。与此相反,过氧化氢依赖性细胞周期停滞与PrxII的过氧化反应,这导致在定量招聘的1666-和140 kD PrxII复合物成大的丝状寡聚体。细胞周期蛋白D1的表达和细胞增殖没有恢复,直到PrxII-SO2 H减少和天然PrxII复合物再生。PrxI或-II的异位表达增加了Prx-SO2 H水平在氧化剂暴露的反应,并未能保护细胞从逮捕。我们提出了一个模型,在该模型中,Prxs作为过氧化物剂量计在亚细胞过程中,涉及氧化还原循环,与过氧化控制结构转变,提醒细胞的扰动过氧化物稳态。
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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