Source:http://linkedlifedata.com/resource/pubmed/id/20498072
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
23
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pubmed:dateCreated |
2010-6-10
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pubmed:abstractText |
Nocturnin (NOC) is a circadian-regulated protein related to the yeast family of transcription factors involved in the cellular response to nutrient status. In mammals, NOC functions as a deadenylase but lacks a transcriptional activation domain. It is highly expressed in bone-marrow stromal cells (BMSCs), hepatocytes, and adipocytes. In BMSCs exposed to the PPAR-gamma (peroxisome proliferator-activated receptor-gamma) agonist rosiglitazone, Noc expression was enhanced 30-fold. Previously, we reported that Noc(-/-) mice had low body temperature, were protected from diet-induced obesity, and most importantly exhibited absence of Pparg circadian rhythmicity on a high-fat diet. Consistent with its role in influencing BMSCs allocation, Noc(-/-) mice have reduced bone marrow adiposity and high bone mass. In that same vein, NOC overexpression enhances adipogenesis in 3T3-L1 cells but negatively regulates osteogenesis in MC3T3-E1 cells. NOC and a mutated form, which lacks deadenylase activity, bind to PPAR-gamma and markedly enhance PPAR-gamma transcriptional activity. Both WT and mutant NOC facilitate nuclear translocation of PPAR-gamma. Importantly, NOC-mediated nuclear translocation of PPAR-gamma is blocked by a short peptide fragment of NOC that inhibits its physical interaction with PPAR-gamma. The inhibitory effect of this NOC-peptide was partially reversed by rosiglitazone, suggesting that effect of NOC on PPAR-gamma nuclear translocation may be independent of ligand-mediated PPAR-gamma activation. In sum, Noc plays a unique role in the regulation of mesenchymal stem-cell lineage allocation by modulating PPAR-gamma activity through nuclear translocation. These data illustrate a unique mechanism whereby a nutrient-responsive gene influences BMSCs differentiation, adipogenesis, and ultimately body composition.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/AG030910,
http://linkedlifedata.com/resource/pubmed/grant/AR45433-12,
http://linkedlifedata.com/resource/pubmed/grant/AR54604-03,
http://linkedlifedata.com/resource/pubmed/grant/AR54604-S2,
http://linkedlifedata.com/resource/pubmed/grant/GM076626,
http://linkedlifedata.com/resource/pubmed/grant/R01 AR045433-14
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1091-6490
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pubmed:author |
pubmed-author:Ackert-BicknellCherylC,
pubmed-author:AdamoMartin LML,
pubmed-author:ClemmonsDavid RDR,
pubmed-author:DourisNicholasN,
pubmed-author:GargNehaN,
pubmed-author:GilbertMisty RMR,
pubmed-author:GreenCarla BCB,
pubmed-author:HorowitzMark CMC,
pubmed-author:KawaiMasanobuM,
pubmed-author:KojimaShihokoS,
pubmed-author:Lecka-CzernikBeataB,
pubmed-author:RosenClifford JCJ
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pubmed:issnType |
Electronic
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pubmed:day |
8
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pubmed:volume |
107
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10508-13
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pubmed:dateRevised |
2011-4-19
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pubmed:meshHeading |
pubmed-meshheading:20498072-Active Transport, Cell Nucleus,
pubmed-meshheading:20498072-Adipogenesis,
pubmed-meshheading:20498072-Animals,
pubmed-meshheading:20498072-Body Composition,
pubmed-meshheading:20498072-Cell Line,
pubmed-meshheading:20498072-Cell Lineage,
pubmed-meshheading:20498072-Circadian Rhythm,
pubmed-meshheading:20498072-Humans,
pubmed-meshheading:20498072-Mice,
pubmed-meshheading:20498072-Mice, Knockout,
pubmed-meshheading:20498072-Nuclear Proteins,
pubmed-meshheading:20498072-Osteoblasts,
pubmed-meshheading:20498072-PPAR gamma,
pubmed-meshheading:20498072-Transcription Factors
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pubmed:year |
2010
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pubmed:articleTitle |
A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-gamma nuclear translocation.
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pubmed:affiliation |
The Musculoskeletal Laboratory, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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