Linked Life Data

12939399

Source:http://linkedlifedata.com/resource/pubmed/id/12939399

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-8-26
pubmed:abstractText
During terminal differentiation of human and murine cells, telomerase activity and parallel transcription of telomerase reverse transcriptase (hTERT) are inhibited. In this study, we used in vitro and in vivo analyses to determine the role of hTERT promoter elements and associated factors during differentiation-induced inhibition of telomerase expression in RD, a human rhabdomyosarcoma cell line. Assay of telomerase enzyme activity, hTERT mRNA, and reporter gene assays confirmed that the hTERT promoter was silenced during 12-O-tetradecanoylphorbol-13-acetate-induced myogenic differentiation of telomerase-positive RD cells. Promoter deletion and mutation analyses revealed that two E-boxes and an AP-2 site present in a 320-bp region of the promoter were essential for the transcriptional activity of the hTERT gene. Electrophoretic mobility shift assays identified several factors that interact with this region of DNA, including the muscle-specific transcription factors Myf5, Myf6, and myogenin and the ubiquitously expressed factors Sp1 and AP-2. Ectopic expression of the E-box binding factors c-Myc and Mad did influence promoter activity in these cells; indeed, the presence of endogenous c-Myc protein was altered after differentiation. Our findings suggest that the acute regulation of hTERT transcription is primarily controlled by E-box elements, which bind a series of factors during the phased phenotypic changes occurring during the differentiation of RD human muscle cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
739-46
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12939399-Binding Sites, pubmed-meshheading:12939399-Cell Differentiation, pubmed-meshheading:12939399-Cell Line, Tumor, pubmed-meshheading:12939399-DNA-Binding Proteins, pubmed-meshheading:12939399-E-Box Elements, pubmed-meshheading:12939399-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12939399-Humans, pubmed-meshheading:12939399-Kruppel-Like Transcription Factors, pubmed-meshheading:12939399-Muscle Cells, pubmed-meshheading:12939399-Mutagenesis, Site-Directed, pubmed-meshheading:12939399-Promoter Regions, Genetic, pubmed-meshheading:12939399-Proto-Oncogene Proteins c-myc, pubmed-meshheading:12939399-Rhabdomyosarcoma, pubmed-meshheading:12939399-Telomerase, pubmed-meshheading:12939399-Tetradecanoylphorbol Acetate, pubmed-meshheading:12939399-Transcription, Genetic, pubmed-meshheading:12939399-Transcription Factors
pubmed:year
2003
pubmed:articleTitle
Telomerase reverse transcriptase promoter regulation during myogenic differentiation of human RD rhabdomyosarcoma cells.
pubmed:affiliation
UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093-0064, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't