Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2007-8-29
pubmed:abstractText
Myc forms an heterodimer with Max and operates as a transcription factor upon binding to specific DNA sites in cellular chromatin. In addition to recruit histone acetylation activity, Myc binds to the positive transcription elongation factor b (P-TEFb) which consists of the cyclin-dependent kinase CKD9 and its regulatory subunit cyclin T. P-TEFb phosphorylates the carboxyl-terminal-domain (CTD) of the larger subunit of RNA polymerase II as well as negative elongation factors allowing efficient transcription elongation. Here, we report that Myc binds, as heterodimer with Max, exclusively the core active P-TEFb complex, and it recruits P-TEFb at Myc targets in vivo. Pharmacological inhibition of P-TEFb by 5.6-di-chloro-1-b-D-ribofuranosyl-bensimidazole (DRB) specifically inhibits expression of Myc-responsive CAD and NUC genes, and impairs the Myc-induced S-phase and apoptosis of quiescent cells grown in low serum. Chromatin immunoprecipitation assays (ChIP) demonstrated co-occupancy of Myc and P-TEFb to CAD and NUC E-boxes, and DRB treatment diminished the density of Pol II phosphorylated on Ser-2 of its CTD. These results indicate that P-TEFb is recruited in vivo to Myc-target promoters and CDK9 activity is an important step for Myc-dependent stimulation of responsive genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2031-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17700062-Animals, pubmed-meshheading:17700062-Apoptosis, pubmed-meshheading:17700062-Cell Cycle, pubmed-meshheading:17700062-Cell Proliferation, pubmed-meshheading:17700062-Cells, Cultured, pubmed-meshheading:17700062-Chromatin Immunoprecipitation, pubmed-meshheading:17700062-Cyclin-Dependent Kinase 9, pubmed-meshheading:17700062-Dichlororibofuranosylbenzimidazole, pubmed-meshheading:17700062-Gene Expression, pubmed-meshheading:17700062-Phosphorylation, pubmed-meshheading:17700062-Positive Transcriptional Elongation Factor B, pubmed-meshheading:17700062-Promoter Regions, Genetic, pubmed-meshheading:17700062-Protein Binding, pubmed-meshheading:17700062-Protein Subunits, pubmed-meshheading:17700062-Proto-Oncogene Proteins c-myc, pubmed-meshheading:17700062-RNA Polymerase II, pubmed-meshheading:17700062-Rats, pubmed-meshheading:17700062-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2007
pubmed:articleTitle
P-TEFb is a crucial co-factor for Myc transactivation.
pubmed:affiliation
Department of Structural and Functional Biology, University of Naples Federico II, Naples, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't