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PMID: 7745710 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator.

Journal of virology ·Vol. 69 ·No. 6 ·1995-06-00 ·Pages 3624-30

Marshall D, Sample C

Abstract

Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is one of five viral nuclear proteins that are essential for EBV-induced immortalization of primary human B lymphocytes in vitro. Previous studies have implied that EBNA-3C acts as a transcription factor. Using transient transfection assays, we demonstrate that EBNA-3C has two effects on reporter genes that are linked to the latent membrane protein 1 promoter, (i) low-level activation by EBNA-3C alone, as well as potentiation of EBNA-2-mediated transactivation, and (ii) inhibition of the normally strong activation mediated by EBNA-2. These two disparate effects seem to be mediated at different stages following cell feeding. The inhibitory effect of EBNA-3C was localized to a known EBNA-2 response element that had previously been shown to be recognized by the DNA-binding protein RBP-J kappa. In addition, direct interaction between RBP-J kappa and EBNA-3C was observed by coimmunoprecipitation. Activation by EBNA-3C, however, seems to be achieved via sequences that are distinct from RBP-J kappa sites, since activation remained even after these sites had been mutated. Consistent with its ability to activate transcription, a region of EBNA-3C which has homology to the glutamine-rich activation domain of Sp1 can function as a transcription activation domain when it is fused to the heterologous DNA-binding domain of Gal4 and can partially restore the activity of a mutant EBNA-2 protein with a deletion in the transactivation domain. Collectively, these data strongly support the role of EBNA-3C as a transcriptional regulator.

MeSH Terms
Antigens, Viral/genetics,metabolism Cell Line DNA-Binding Proteins/genetics,metabolism Epstein-Barr Virus Nuclear Antigens Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein Nuclear Proteins Promoter Regions, Genetic Protein Binding Trans-Activators/metabolism Transcriptional Activation Viral Matrix Proteins/genetics
Chemicals
Antigens, Viral DNA-Binding Proteins EBV-associated membrane antigen, Epstein-Barr virus Epstein-Barr Virus Nuclear Antigens Immunoglobulin J Recombination Signal Sequence-Binding Protein Nuclear Proteins RBPJ protein, human Trans-Activators Viral Matrix Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Marshall D
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Sample C
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.69.6.3624-3630.1995
Published
1995-06-00
Pages
3624-30
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC189077
Subset
IM
Grants
NCI NIH HHS · R01 CA056645 · United States
NCI NIH HHS · CA-21765 · United States
NCI NIH HHS · CA-56645 · United States
External Links
PubMed source DOI: 10.1128/JVI.69.6.3624-3630.1995 PMC Full Text View journal details
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