Nuclear and cytoplasmic peroxiredoxin-1 differentially regulate NF-kappaB activities.
Peroxiredoxins (Prx) are widely distributed and abundant proteins, which control peroxide concentrations and related signaling mechanisms. Prx1 is found in the cytoplasm and nucleus, but little is known about compartmentalized Prx1 function during redox signaling and oxidative stress. We targeted expression vectors to increase Prx1 in nuclei (NLS-Prx1) and cytoplasm (NES-Prx1) in HeLa cells. Results showed that NES-Prx1 inhibited NF-kappaB activation and nuclear translocation. In contrast, increased NLS-Prx1 did not affect NF-kappaB nuclear translocation but increased activity of a NF-kappaB reporter. Both NLS-Prx1 and NES-Prx1 inhibited NF-kappaB p50 oxidation, suggesting that oxidation of the redox-sensitive cysteine in p50's DNA-binding domain is regulated via peroxide metabolism in both compartments. Interestingly, following treatment with H(2)O(2), nuclear thioredoxin-1 (Trx1) redox status was protected by NLS-Prx1, and cytoplasmic Trx1 was protected by NES-Prx1. Compartmental differences from increasing Prx1 show that the redox poise of cytoplasmic and nuclear thiol systems can be dynamically controlled through peroxide elimination. Such spatial resolution and protein-specific redox differences imply that the balance of peroxide generation/metabolism in microcompartments provides an important specific component of redox signaling.
Hansen
Jason M
JM
Department of Pediatrics, Emory School of Medicine, Emory University, 2015 Uppergate Drive #350, Atlanta, GA 30322, USA. jhansen@emory.edu
Moriarty-Craige
Siobhan
S
Jones
Dean P
DP
D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D017930:Genes, Reporter; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D011994:Recombinant Proteins / Q000378:metabolism
D016328:NF-kappa B; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D010544:Peroxidases; C515940:PRDX1 protein, human; D054464:Peroxiredoxins