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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28
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pubmed:dateCreated |
2007-7-9
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pubmed:abstractText |
Transforming growth factor-beta (TGF-beta) signaling is controlled by a variety of regulators that target either signaling receptors or activated Smad complexes. Among the negative regulators, Smad7 antagonizes TGF-beta signaling mainly through targeting the signaling receptors, whereas SnoN and c-Ski repress signaling at the transcriptional level through inactivation of Smad complexes. We previously found that Arkadia is a positive regulator of TGF-beta signaling that induces ubiquitin-dependent degradation of Smad7 through its C-terminal RING domain. We report here that Arkadia induces degradation of SnoN and c-Ski in addition to Smad7. Arkadia interacts with SnoN and c-Ski in their free forms as well as in the forms bound to Smad proteins, and constitutively down-regulates levels of their expression. Arkadia thus appears to effectively enhance TGF-beta signaling through simultaneous down-regulation of two distinct types of negative regulators, Smad7 and SnoN/c-Ski, and may play an important role in determining the intensity of TGF-beta family signaling in target cells.
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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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Rnf111 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/SKI protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SKIL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad7 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:EpiskopouVassoV,
pubmed-author:FujiiTomokoT,
pubmed-author:ImamuraTakeshiT,
pubmed-author:IsogayaKazunobuK,
pubmed-author:KoinumaDaizoD,
pubmed-author:LeeKian LeongKL,
pubmed-author:MavrakisKonstantinos JKJ,
pubmed-author:MiyazawaKeijiK,
pubmed-author:MiyazonoKoheiK,
pubmed-author:NaganoYoshikoY,
pubmed-author:SaitohMasaoM,
pubmed-author:SaseHitoshiH,
pubmed-author:YukiKeikoK
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20492-501
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pubmed:dateRevised |
2011-10-24
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pubmed:meshHeading |
pubmed-meshheading:17510063-Animals,
pubmed-meshheading:17510063-COS Cells,
pubmed-meshheading:17510063-Cercopithecus aethiops,
pubmed-meshheading:17510063-DNA-Binding Proteins,
pubmed-meshheading:17510063-Down-Regulation,
pubmed-meshheading:17510063-HeLa Cells,
pubmed-meshheading:17510063-Humans,
pubmed-meshheading:17510063-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17510063-Mice,
pubmed-meshheading:17510063-Protein Binding,
pubmed-meshheading:17510063-Proto-Oncogene Proteins,
pubmed-meshheading:17510063-Signal Transduction,
pubmed-meshheading:17510063-Smad7 Protein,
pubmed-meshheading:17510063-Transcription, Genetic,
pubmed-meshheading:17510063-Transforming Growth Factor beta,
pubmed-meshheading:17510063-Ubiquitin,
pubmed-meshheading:17510063-Ubiquitin-Protein Ligases
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pubmed:year |
2007
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pubmed:articleTitle |
Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling.
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pubmed:affiliation |
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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