Document Detail


Role for Prdx1 as a specific sensor in redox-regulated senescence in breast cancer.
MedLine Citation:
PMID:  23334324     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent studies suggest that Peroxiredoxin 1 (Prdx1), in addition to its known H₂O₂-scavenging function, mediates cell signaling through redox-specific protein-protein interactions. Our data illustrate how Prdx1 specifically coordinates p38MAPK-induced signaling through regulating p38MAPKα phosphatases in an H₂O₂ dose-dependent manner. MAPK phosphatases (MKP-1 and/or MKP-5), which are known to dephosphorylate and deactivate the senescence-inducing MAPK p38α, belong to a group of redox-sensitive phosphatases (protein tyrosine phosphatases) characterized by a low pKa cysteine in their active sites. We found that Prdx1 bound to both MKP-1 and MKP-5, but dissociated from MKP-1 when the Prdx1 peroxidatic cysteine Cys52 was over-oxidized to sulfonic acid, which in turn resulted in MKP-1 oxidation-induced oligomerization and inactivity toward p38MAPKα. Conversely, over-oxidation of Prdx1-Cys52 was enhancing in the Prdx1:MKP-5 complex with increasing amounts of H₂O₂ concentrations and correlated with a protection from oxidation-induced oligomerization and inactivation of MKP-5 so that activation toward p38MAPK was maintained. Further examination of this Prdx1-specific mechanism in a model of reactive oxygen species-induced senescence of human breast epithelial cells revealed the specific activation of MKP-5, resulting in decreased p38MAPKα activity. Taken together, our data suggest that Prdx1 orchestrates redox signaling in an H₂O₂ dose-dependent manner through the oxidation status of its peroxidatic cysteine Cys52.
Authors:
B Turner-Ivey; Y Manevich; J Schulte; E Kistner-Griffin; A Jezierska-Drutel; Y Liu; C A Neumann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-01-21
Journal Detail:
Title:  Oncogene     Volume:  32     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-07     Completed Date:  2014-01-08     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  5302-14     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / metabolism*
Cell Aging*
Cell Line, Tumor
Dual Specificity Phosphatase 1 / metabolism
Dual-Specificity Phosphatases / metabolism*
Enzyme Activation
Epithelial Cells / metabolism
Female
HEK293 Cells
Humans
Hydrogen Peroxide / metabolism
MAP Kinase Signaling System
MCF-7 Cells
Mitogen-Activated Protein Kinase Phosphatases / metabolism*
Oxidation-Reduction
Peroxiredoxins / metabolism*
Reactive Oxygen Species
p38 Mitogen-Activated Protein Kinases / metabolism*
Grant Support
ID/Acronym/Agency:
5T32 CA119945-05/CA/NCI NIH HHS; K22 ES012985-01/ES/NIEHS NIH HHS; P30 CA138313/CA/NCI NIH HHS; R01 CA131350/CA/NCI NIH HHS; R01 CA131350/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; BBX060AN9V/Hydrogen Peroxide; EC 1.11.1.15/PRDX1 protein, human; EC 1.11.1.15/Peroxiredoxins; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.1.3.-/Mitogen-Activated Protein Kinase Phosphatases; EC 3.1.3.16/DUSP10 protein, human; EC 3.1.3.48/DUSP1 protein, human; EC 3.1.3.48/Dual Specificity Phosphatase 1; EC 3.1.3.48/Dual-Specificity Phosphatases
Comments/Corrections

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