Document Detail


Cytoplasmic localization and ubiquitination of p21(Cip1) by reactive oxygen species.
MedLine Citation:
PMID:  17477906     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Reactive oxygen species were previously shown to trigger p21(Cip1) protein degradation through a proteasome-dependent pathway, however the detailed mechanism of degradation remains to be elucidated. In this report, we showed that p21(Cip1) was degraded at an early phase after low dose H(2)O(2) treatment of a variety of cell types and that preincubation of cells with the antioxidant, N-acetylcysteine, prolonged p21(Cip1) half-life. A mutant p21(Cip1) in which all six lysines were changed to arginines was protected against H(2)O(2) treatment. Direct interaction between p21(Cip1) and Skp2 was elevated in the H(2)O(2)-treated cells. Disruption of the two nuclear export signal (NES) sequences in p21(Cip1), or treatment with leptomycin B blocked H(2)O(2)-induced p21(Cip1) degradation. Altogether, these results demonstrate that reactive oxygen species induce p21(Cip1) degradation through an NES-, Skp2-, and ubiquitin-dependent pathway.
Authors:
Chae Young Hwang; Ick Young Kim; Ki-Sun Kwon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-25
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  358     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-15     Completed Date:  2007-07-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  219-25     Citation Subset:  IM    
Affiliation:
Laboratory of Cell Signaling, Proteome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / pharmacology
Amino Acid Sequence
Amino Acid Substitution
Animals
Antioxidants / pharmacology
Cell Line
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism*
Cytoplasm / metabolism*
Fatty Acids, Unsaturated / pharmacology
Humans
Hydrogen Peroxide / pharmacology
Molecular Sequence Data
Nuclear Export Signals
Reactive Oxygen Species / metabolism*
S-Phase Kinase-Associated Proteins / metabolism
Ubiquitin / metabolism*
Chemical
Reg. No./Substance:
0/Antioxidants; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Fatty Acids, Unsaturated; 0/Nuclear Export Signals; 0/Reactive Oxygen Species; 0/S-Phase Kinase-Associated Proteins; 0/Ubiquitin; 616-91-1/Acetylcysteine; 7722-84-1/Hydrogen Peroxide; 87081-35-4/leptomycin B

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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