Linked Life Data

18342333

Source:http://linkedlifedata.com/resource/pubmed/id/18342333

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-4-3
pubmed:abstractText
Hepatitis B virus (HBV) is a causative agent of chronic hepatitis and hepatocellular carcinoma. Recent findings demonstrating p73 and specifically N-terminally truncated p73 (DeltaTAp73) accumulation in hepatocellular carcinoma suggest that p73 plays a role in the malignant phenotype. Here, we investigated the mechanism of HBV pregenomic core promoter/enhancer II (cp/EII) regulation by full-length TAp73 and its oncogenic counterpart DeltaTAp73. Ectopic and endogenous expression of TAp73 leads to a significant downregulation of cp/EII activity in p53-deficient hepatoma cell lines. In contrast, overexpression of DeltaTAp73 results in significant cp/EII activation and increased HBV core (HBc) expression. TAp73-mediated repression of HBV transcription was substantially abolished by DeltaTAp73. We show that both TAp73 and DeltaTAp73 proteins directly bind to the Sp1 transcription factor, a key stimulator of HBV gene expression. However, only TAp73 abolishes Sp1 binding to cp/EII, whereas the DeltaTAp73-Sp1 complex further persists on the DNA. The inhibitory effect of p53/p73 on HBc expression is associated with the inhibition of viral replication, while DeltaTAp73 is not. These data strongly support the fact that the p73-isoform-related interaction with Sp1 is the underlying mechanism of the diverse outcome on HBc expression, suggesting a new mechanism by which oncogenic DeltaTAp73 could enhance the carcinogenic process in liver cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1089-8638
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
378
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20-30
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18342333-Cell Transformation, Viral, pubmed-meshheading:18342333-DNA-Binding Proteins, pubmed-meshheading:18342333-Enhancer Elements, Genetic, pubmed-meshheading:18342333-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18342333-Gene Expression Regulation, Viral, pubmed-meshheading:18342333-Hepatitis B virus, pubmed-meshheading:18342333-Humans, pubmed-meshheading:18342333-Liver Neoplasms, pubmed-meshheading:18342333-Nuclear Proteins, pubmed-meshheading:18342333-Promoter Regions, Genetic, pubmed-meshheading:18342333-Protein Isoforms, pubmed-meshheading:18342333-Sp1 Transcription Factor, pubmed-meshheading:18342333-Transcription, Genetic, pubmed-meshheading:18342333-Tumor Suppressor Proteins, pubmed-meshheading:18342333-Viral Core Proteins, pubmed-meshheading:18342333-Virus Replication
pubmed:year
2008
pubmed:articleTitle
Molecular mechanism of p73-mediated regulation of hepatitis B virus core promoter/enhancer II: implications for hepatocarcinogenesis.
pubmed:affiliation
Department of Vectorology and Experimental Gene Therapy, Biomedical Research Center, University of Rostock, Schillingallee 69, D-18057 Rostock, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't