Source:http://linkedlifedata.com/resource/pubmed/id/19911008
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2010-3-15
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| pubmed:abstractText |
Post-translational modification and degradation of proteins by the ubiquitin-proteasome system are key regulatory mechanisms in cellular responses to various stimuli. The NF-kappaB signaling pathway is controlled by the ubiquitin-mediated proteolysis. RelA/p65, which is a main subunit of NF-kappaB, is ubiquitinated for degradation by SOCS-1, but the functional mechanism of its ubiquitination remains poorly understood. In this study we show that phosphorylation of RelA/p65 at Ser276 prevents its degradation by ubiquitin-mediated proteolysis. In contrast, impairment of Ser276 phosphorylation affects constitutive degradation of RelA/p65. Importantly, we identify Pim-1 as a further kinase responsible for the phosphorylation of RelA/p65 at Ser276. Depletion of Pim-1 hinders not only Ser276 phosphorylation but also transactivation of RelA/p65 target genes. We also show that Pim-1 contributes to recruitment of RelA/p65 to kappaB-elements to activate NF-kappaB signalling after TNF-alpha stimulation. In concert with these results, the knockdown of Pim-1 impairs IL-6 production and augments apoptosis by interfering RelA/p65 activation. These findings provide a model in which Pim-1 phosphorylation of RelA/p65 at Ser276 allows defense against ubiquitin-mediated degradation and whereby exerts activation of NF-kappaB signalling.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-pim-1,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
1476-5403
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
17
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
689-98
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| pubmed:meshHeading |
pubmed-meshheading:19911008-Amino Acid Sequence,
pubmed-meshheading:19911008-Animals,
pubmed-meshheading:19911008-Apoptosis,
pubmed-meshheading:19911008-COS Cells,
pubmed-meshheading:19911008-Cercopithecus aethiops,
pubmed-meshheading:19911008-Down-Regulation,
pubmed-meshheading:19911008-Gene Expression Regulation,
pubmed-meshheading:19911008-HeLa Cells,
pubmed-meshheading:19911008-Humans,
pubmed-meshheading:19911008-Interleukin-6,
pubmed-meshheading:19911008-NF-kappa B,
pubmed-meshheading:19911008-Phosphorylation,
pubmed-meshheading:19911008-Proto-Oncogene Proteins c-pim-1,
pubmed-meshheading:19911008-RNA Interference,
pubmed-meshheading:19911008-Serine,
pubmed-meshheading:19911008-Signal Transduction,
pubmed-meshheading:19911008-Transcription Factor RelA,
pubmed-meshheading:19911008-Transcriptional Activation,
pubmed-meshheading:19911008-Tumor Necrosis Factor-alpha,
pubmed-meshheading:19911008-Ubiquitin
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| pubmed:year |
2010
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| pubmed:articleTitle |
Pim-1 controls NF-kappaB signalling by stabilizing RelA/p65.
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| pubmed:affiliation |
Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8510, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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