rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2009-8-27
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pubmed:abstractText |
Menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, is involved in activation of gene transcription as part of an MLL1 (mixed-lineage leukemia 1)/MLL2 (KMT2A/B)-containing protein complex which harbors methyltransferase activity for lysine 4 of histone H3 (H3K4). As MEN1 patients frequently develop lipomas and peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in several MEN1-related tumor types, we investigated regulation of PPARgamma activity by menin. We found that menin is required for adipocyte differentiation of murine 3T3-L1 cells and PPARgamma-expressing mouse embryonic fibroblasts. Menin augments PPARgamma target gene expression through recruitment of H3K4 methyltransferase activity. Menin interacts directly with the activation function 2 transcription activation domain of PPARgamma in a ligand-independent fashion. Ligand-dependent coactivation, however, is dependent on the LXXLL motif of menin and the intact helix 12 of PPARgamma. We propose that menin is an important factor in PPARgamma-mediated adipogenesis and that loss of PPARgamma function may contribute to lipoma development in MEN1 patients.
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pubmed:commentsCorrections |
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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/FABP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acid-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/MEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Men1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1098-5549
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5060-9
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pubmed:dateRevised |
2010-9-24
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pubmed:meshHeading |
pubmed-meshheading:19596783-3T3-L1 Cells,
pubmed-meshheading:19596783-Adipocytes,
pubmed-meshheading:19596783-Animals,
pubmed-meshheading:19596783-Cell Differentiation,
pubmed-meshheading:19596783-Fatty Acid-Binding Proteins,
pubmed-meshheading:19596783-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19596783-Gene Knockdown Techniques,
pubmed-meshheading:19596783-Histones,
pubmed-meshheading:19596783-Humans,
pubmed-meshheading:19596783-Ligands,
pubmed-meshheading:19596783-Lysine,
pubmed-meshheading:19596783-Methylation,
pubmed-meshheading:19596783-Mice,
pubmed-meshheading:19596783-PPAR gamma,
pubmed-meshheading:19596783-Protein Binding,
pubmed-meshheading:19596783-Protein Structure, Tertiary,
pubmed-meshheading:19596783-Proto-Oncogene Proteins,
pubmed-meshheading:19596783-Transcription, Genetic
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pubmed:year |
2009
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pubmed:articleTitle |
The multiple endocrine neoplasia type 1 (MEN1) tumor suppressor regulates peroxisome proliferator-activated receptor gamma-dependent adipocyte differentiation.
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pubmed:affiliation |
University Medical Center Utrecht, Department of Physiological Chemistry, Utrecht, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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