Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-9-30
pubmed:abstractText
Multiple epidemiologic studies show that adeno-associated virus (AAV) is negatively associated with cervical cancer (CX CA), a cancer which is positively associated with human papillomavirus (HPV) infection. Mechanisms for this correlation may be by Rep78's (AAV's major regulatory protein) ability to bind the HPV-16 p97 promoter DNA and inhibit transcription, to bind and interfere with the functions of the E7 oncoprotein of HPV-16, and to bind a variety of HPV-important cellular transcription factors such as Sp1 and TBP. c-Jun is another important cellular factor intimately linked to the HPV life cycle, as well as keratinocyte differentiation and skin development. Skin is the natural host tissue for both HPV and AAV. In this article it is demonstrated that Rep78 directly interacts with c-Jun, both in vitro and in vivo, as analyzed by Western blot, yeast two-hybrid cDNA, and electrophoretic mobility shift-supershift assay (EMSA supershift). Addition of anti-Rep78 antibodies inhibited the EMSA supershift. Investigating the biological implications of this interaction, Rep78 inhibited the c-Jun-dependent c-jun promoter in transient and stable chloramphenicol acetyl-transferase (CAT) assays. Rep78 also inhibited c-Jun-augmented c-jun promoter as well as the HPV-16 p97 promoter activity (also c-Jun regulated) in in vitro transcription assays in T47D nuclear extracts. Finally, the Rep78-c-Jun interaction mapped to the amino-half of Rep78. The ability of Rep78 to interact with c-Jun and down-regulate AP-1-dependent transcription suggests one more mechanism by which AAV may modulate the HPV life cycle and the carcinogenesis process.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-31
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14517094-Blotting, Western, pubmed-meshheading:14517094-DNA-Binding Proteins, pubmed-meshheading:14517094-Dependovirus, pubmed-meshheading:14517094-Down-Regulation, pubmed-meshheading:14517094-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:14517094-Gene Expression Regulation, Viral, pubmed-meshheading:14517094-HeLa Cells, pubmed-meshheading:14517094-Humans, pubmed-meshheading:14517094-Papillomaviridae, pubmed-meshheading:14517094-Promoter Regions, Genetic, pubmed-meshheading:14517094-Protein Binding, pubmed-meshheading:14517094-Proto-Oncogene Proteins c-jun, pubmed-meshheading:14517094-Transcription, Genetic, pubmed-meshheading:14517094-Transcription Factor AP-1, pubmed-meshheading:14517094-Two-Hybrid System Techniques, pubmed-meshheading:14517094-Viral Proteins
pubmed:year
2003
pubmed:articleTitle
The adeno-associated virus major regulatory protein Rep78-c-Jun-DNA motif complex modulates AP-1 activity.
pubmed:affiliation
Department of Internal Medicine, Gene Therapy Center for Molecular Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.