Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery.
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 approximately 66- and approximately 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.
Phalen
Timothy J
TJ
Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Weirather
Kelly
K
Deming
Paula B
PB
Anathy
Vikas
V
Howe
Alan K
AK
van der Vliet
Albert
A
Jönsson
Thomas J
TJ
Poole
Leslie B
LB
Heintz
Nicholas H
NH
D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010544:Peroxidases / Q000737:chemistry* / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism*; D054464:Peroxiredoxins; D044967:Serum / Q000502:physiology; D015398:Signal Transduction
D010545:Peroxides; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins