Linked Life Data

15226182

Source:http://linkedlifedata.com/resource/pubmed/id/15226182

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2004-10-6
pubmed:abstractText
In immortal cells, the existence of a mechanism for the maintenance of telomere length is critical. In most cases this is achieved by the reactivation of telomerase, a cellular reverse transcriptase that prevents telomere shortening. Here we report that the telomerase gene (hTERT) promoter is up-regulated during transmission of human T-cell lymphotropic virus type-I (HTLV-I) to primary T cells in vitro and in ex vivo adult T-cell leukemia/lymphoma (ATLL) samples, but not asymptomatic carriers. Although Tax impaired induction of human telomerase reverse transcriptase (hTERT) mRNA in response to mitogenic stimulation, transduction of Tax into primary lymphocytes was sufficient to activate and maintain telomerase expression and telomere length when cultured in the absence of any exogenous stimulation. Transient transfection assays revealed that Tax stimulates the hTERT promoter through the nuclear factor kappaB (NF-kappaB) pathway. Consistently, Tax mutants inactive for NF-kappaB activation could not activate the hTERT or sustain telomere length in transduced primary lymphocytes. Analysis of the hTERT promoter occupancy in vivo using chromatin immunoprecipitation assays suggested that an increased binding of c-Myc and Sp1 is involved in the NF-kappaB-mediated activation of the hTERT promoter. This study establishes the role of Tax in regulation of telomerase expression, which may cooperate with other functions of Tax to promote HTLV-I-associated adult T-cell leukemia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2523-31
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed-meshheading:15226182-Cell Line, Transformed, pubmed-meshheading:15226182-Cells, Cultured, pubmed-meshheading:15226182-Chromatin, pubmed-meshheading:15226182-DNA-Binding Proteins, pubmed-meshheading:15226182-Gene Products, tax, pubmed-meshheading:15226182-Human T-lymphotropic virus 1, pubmed-meshheading:15226182-Humans, pubmed-meshheading:15226182-Leukemia-Lymphoma, Adult T-Cell, pubmed-meshheading:15226182-Lymphocyte Activation, pubmed-meshheading:15226182-Models, Genetic, pubmed-meshheading:15226182-NF-kappa B, pubmed-meshheading:15226182-Promoter Regions, Genetic, pubmed-meshheading:15226182-Proto-Oncogene Proteins c-myc, pubmed-meshheading:15226182-RNA, Messenger, pubmed-meshheading:15226182-Sp1 Transcription Factor, pubmed-meshheading:15226182-T-Lymphocytes, pubmed-meshheading:15226182-Telomerase, pubmed-meshheading:15226182-Transcription, Genetic, pubmed-meshheading:15226182-Transcriptional Activation
pubmed:year
2004
pubmed:articleTitle
Transcriptional activation of hTERT through the NF-kappaB pathway in HTLV-I-transformed cells.
pubmed:affiliation
University of Kansas Medical Center, Department of Microbiology, Immunology, and Molecular Genetics, 3025 Wahl Hall West, 3901 Rainbow Blvd, Kansas City, KS 66160, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't