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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
47
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pubmed:dateCreated |
2004-11-15
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pubmed:abstractText |
Treatment with the stress agent prostaglandin A2 (PGA2) induces expression of the cyclin-dependent kinase inhibitor p21. Here, we present evidence that p21 expression increases through PGA2-triggered stabilization of the p21 mRNA and further show that these events require the mitogen-activated protein (MAP) kinase ERK. Binding experiments using either endogenous p21 mRNA or in vitro-labeled p21 transcripts revealed a specific PGA2-dependent association of the p21 mRNA with the RNA-binding protein HuR. Interestingly, although inhibition of the ERK pathway did not prevent the PGA2-triggered increase in cytoplasmic HuR, it did impair the formation of endogenous and in vitro [HuR-p21 mRNA] complexes and further prevented the PGA2-mediated stabilization of the p21 mRNA, suggesting that ERK-mediated events were required for binding HuR to the p21 mRNA and preventing its decay. RNA interference-based knockdown of HuR abundance further served to demonstrate the contribution of HuR-mediated p21 mRNA stabilization toward enhancing p21 expression after PGA2 treatment. Collectively, our results indicate that PGA2 stabilizes the p21 mRNA through an ERK-independent increase in cytoplasmic HuR levels and an ERK-dependent association of HuR with the p21 mRNA.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Biotin,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/ELAVL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandins A,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/prostaglandin A2
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
49298-306
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15371446-3' Untranslated Regions,
pubmed-meshheading:15371446-Antigens, Surface,
pubmed-meshheading:15371446-Biotin,
pubmed-meshheading:15371446-Blotting, Northern,
pubmed-meshheading:15371446-Blotting, Western,
pubmed-meshheading:15371446-Calcium,
pubmed-meshheading:15371446-Cell Cycle Proteins,
pubmed-meshheading:15371446-Cell Line, Tumor,
pubmed-meshheading:15371446-Cell Nucleus,
pubmed-meshheading:15371446-Cell Proliferation,
pubmed-meshheading:15371446-Cross-Linking Reagents,
pubmed-meshheading:15371446-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:15371446-Cytoplasm,
pubmed-meshheading:15371446-DNA, Complementary,
pubmed-meshheading:15371446-Dactinomycin,
pubmed-meshheading:15371446-Dose-Response Relationship, Drug,
pubmed-meshheading:15371446-Enzyme Inhibitors,
pubmed-meshheading:15371446-Humans,
pubmed-meshheading:15371446-Immunoprecipitation,
pubmed-meshheading:15371446-Kinetics,
pubmed-meshheading:15371446-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:15371446-Prostaglandins A,
pubmed-meshheading:15371446-Protein Binding,
pubmed-meshheading:15371446-RNA, Messenger,
pubmed-meshheading:15371446-RNA-Binding Proteins,
pubmed-meshheading:15371446-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15371446-Signal Transduction,
pubmed-meshheading:15371446-Time Factors,
pubmed-meshheading:15371446-Transfection,
pubmed-meshheading:15371446-Ultraviolet Rays
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pubmed:year |
2004
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pubmed:articleTitle |
Prostaglandin A2-mediated stabilization of p21 mRNA through an ERK-dependent pathway requiring the RNA-binding protein HuR.
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pubmed:affiliation |
Laboratory of Cellular and Molecular Biology, NIA, National Institutes of Health, Baltimore, MD 21224, USA.
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pubmed:publicationType |
Journal Article
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