|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
3-4
|
|
pubmed:dateCreated |
2006-6-7
|
|
pubmed:abstractText |
Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor alpha (RXRalpha) and retinoic acid receptor alpha (RARalpha) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRalpha/RARalpha/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRalpha/RARalpha/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoid X Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/p300-CBP Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/pyruvate dehydrogenase...,
http://linkedlifedata.com/resource/pubmed/chemical/pyruvate dehydrogenase kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
|
|
pubmed:status |
MEDLINE
|
|
pubmed:issn |
0006-3002
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
1759
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
141-51
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:16757381-Acetylation,
pubmed-meshheading:16757381-Cell Line,
pubmed-meshheading:16757381-Enzyme Inhibitors,
pubmed-meshheading:16757381-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:16757381-Histone Deacetylase Inhibitors,
pubmed-meshheading:16757381-Histone Deacetylases,
pubmed-meshheading:16757381-Histones,
pubmed-meshheading:16757381-Humans,
pubmed-meshheading:16757381-Hydroxamic Acids,
pubmed-meshheading:16757381-Molecular Sequence Data,
pubmed-meshheading:16757381-Promoter Regions, Genetic,
pubmed-meshheading:16757381-Protein Binding,
pubmed-meshheading:16757381-Protein Kinases,
pubmed-meshheading:16757381-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16757381-Receptors, Retinoic Acid,
pubmed-meshheading:16757381-Response Elements,
pubmed-meshheading:16757381-Retinoid X Receptor alpha,
pubmed-meshheading:16757381-Transcription, Genetic,
pubmed-meshheading:16757381-Transcriptional Activation,
pubmed-meshheading:16757381-Tretinoin,
pubmed-meshheading:16757381-p300-CBP Transcription Factors
|
|
pubmed:articleTitle |
Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression.
|
|
pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive MS 4053, Indianapolis, IN 46202-5122, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
