Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-10-22
pubmed:abstractText
c-JUN is a major component of heterodimer transcription factor AP-1 (Activator Protein-1) that activates gene transcription in cell proliferation, inflammation and stress responses. SIRT1 (Sirtuin 1) is a histone deacetylase that controls gene transcription through modification of chromatin structure. However, it is not clear if SIRT1 regulates c-JUN activity in the control of gene transcription. Here, we show that SIRT1 associated with c-JUN in co-immunoprecipitation of whole cell lysate, and inhibited the transcriptional activity of c-JUN in the mammalian two hybridization system. SIRT1 was found in the AP-1 response element in the matrix metalloproteinase-9 (MMP9) promoter DNA leading to inhibition of histone 3 acetylation as shown in a ChIP assay. The SIRT1 signal was reduced by the AP-1 activator PMA, and induced by the SIRT1 activator Resveratrol in the promoter DNA. SIRT1-mediaetd inhibition of AP-1 was demonstrated in the MMP9 gene expression at the gene promoter, mRNA and protein levels. In mouse embryonic fibroblast (MEF) with SIRT1 deficiency (SIRT1(-/-)), mRNA and protein of MMP9 were increased in the basal condition, and the inhibitory activity of Resveratrol was significantly attenuated. Glucose-induced MMP9 expression was also inhibited by SIRT1 in response to Resveratrol. These data consistently suggest that SIRT1 directly inhibits the transcriptional activity of AP-1 by targeting c-JUN.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-10935492, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-11087751, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-12213555, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-12351658, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-12939617, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-12960381, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-14661062, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-15213027, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-15269222, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-15277439, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-15604409, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-15744310, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-15811852, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-16150801, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-16183991, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-16246065, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-17908551, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-18046409, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-18423418, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-18577374, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-8631874, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-9115218, http://linkedlifedata.com/resource/pubmed/commentcorrection/18823944-9590175
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
376
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
793-6
pubmed:dateRevised
2011-5-2
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Inhibition of transcriptional activity of c-JUN by SIRT1.
pubmed:affiliation
Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural