Linked Life Data

12466474

Source:http://linkedlifedata.com/resource/pubmed/id/12466474

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 12
pubmed:dateCreated
2002-12-5
pubmed:abstractText
Productive infection of non-proliferating cells by cytomegalovirus (CMV) requires the coordinated stimulation of host biochemical pathways that prepare cells to synthesize DNA. Here we illustrate the ability of human CMV (HCMV) to stimulate cellular thymidylate synthase (TS) gene expression in quiescent human embryonic lung fibroblasts. TS mRNA and protein levels are nearly undetectable in quiescent cells, but are greatly increased following HCMV infection. Inhibition of TS activity was shown to impair HCMV DNA synthesis, demonstrating that TS upregulation is required for efficient HCMV replication in quiescent cells. The increase in TS gene expression was due to an increase in gene transcription, since the expression of a reporter gene driven by the human TS promoter was strongly induced by HCMV infection. Deletion analysis of the human TS promoter identified two positive elements that are important for this increased transcription. We have previously shown that murine CMV (MCMV) stimulates the mouse TS promoter by a mechanism that depends on the presence of an E2F element in the promoter region. However, deletion of the two potential E2F binding sites in the human TS promoter did not prevent the virus-induced increase in TS promoter activity. Our data suggest that HCMV activates human TS gene transcription by mechanisms that are independent of E2F and different from those used by MCMV to stimulate the mouse TS promoter.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1317
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2983-93
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Human cytomegalovirus infection induces cellular thymidylate synthase gene expression in quiescent fibroblasts.
pubmed:affiliation
Department of Public Health and Microbiology, University of Torino, Via Santena, 9 - 10126 Torino, Italy. giorgio.girbaudo@unito.it
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't