Linked Life Data

12379483

Source:http://linkedlifedata.com/resource/pubmed/id/12379483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-10-15
pubmed:abstractText
Among the hepatotropic viruses, hepatitis C virus (HCV) is considered to be the leading cause of liver disease in humans, affecting approximately 2% of the world population. HCV-encoded nonstructural protein 5A (NS5A) is a 56-58-kDa phosphoprotein, which is produced from the processing of viral polyprotein. The potential mechanism(s) by which NS5A is able to influence key cellular processes are largely unknown. In this study, we investigated the functional properties of NS5A. In vivo co-immunoprecipitation and pull-down assays demonstrated that NS5A forms a heteromeric complex with TATA box binding protein (TBP) and tumor suppressor protein p53. Mutants of TBP and p53 showed reduced binding to NS5A. To determine the functional relevance of these associations, we found that NS5A inhibits the binding of both p53 and TBP to their DNA consensus binding sequences in vitro. NS5A also inhibited the p53-TBP and p53-excision repair cross complementing factor 3 (ERCC3) protein-protein complex formation. Furthermore, NS5A repressed the p53 regulated p21 (WAF1) promoter and a synthetic promoter containing multiple p53 responsive DNA elements binding sites in HCT116 p53(+/+) cell line. p53-mediated transcriptional activation from both promoters was reduced approximately 3-5-fold following expression of NS5A. Taken together, these results suggest that NS5A may exert its influence on key cellular processes by functional associations with p53 and TBP. This could explain one of the possible mechanism(s) by which NS5A is able to exert its effect on cellular gene expression and cell growth regulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
1592
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
193-204
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Hepatitis C virus NS5A protein binds TBP and p53, inhibiting their DNA binding and p53 interactions with TBP and ERCC3.
pubmed:affiliation
Department of Medicine, Division of Gastroenterology and Hepatology, Hepatobiliary Center, University of Colorado Health Sciences Center, B-145, 4200 E., 9th Avenue, Denver 80262, USA. Ishtiaq.qadri@uchsc.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't