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PMID: 9445037 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An ATF/CRE element mediates both EBNA2-dependent and EBNA2-independent activation of the Epstein-Barr virus LMP1 gene promoter.

Journal of virology ·Vol. 72 ·No. 2 ·1998-02-00 ·Pages 1365-76

Sjöblom A, Yang W, Palmqvist L, Jansson A, Rymo L

Abstract

The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is a viral oncogene whose expression is regulated by both viral and cellular factors. EBV nuclear antigen 2 (EBNA2) is a potent transactivator of LMP1 expression in human B cells, and several EBNA2 response elements have been identified in the promoter regulatory sequence (LRS). We have previously shown that an activating transcription factor/cyclic AMP response element (ATF/CRE) site in LRS is involved in EBNA2 responsiveness. We now establish the importance of the ATF/CRE element by mutational analysis and show that both EBNA2-dependent activation and EBNA2-independent activation of the promoter occur via this site but are mediated by separate sets of factors. An electrophoretic mobility shift assay (EMSA) with specific antibodies showed that the ATF-1, CREB-1, ATF-2 and c-Jun factors bind to the site as ATF-1/CREB-1 and ATF-2/c-Jun heterodimers whereas the Sp1 and Sp3 factors bind to an adjacent Sp site. Overexpression of ATF-1 and CREB-1 in the cells by expression vectors demonstrated that homodimeric as well as heterodimeric forms of the factors transactivate the LMP1 promoter in an EBNA2-independent manner. The homodimers of ATF-2 and c-Jun did not significantly stimulate promoter activity. In contrast, the ATF-2/c-Jun heterodimer had only a minor stimulatory effect in the absence of EBNA2 but induced a strong transactivation of the LMP1 promoter when coexpressed with this protein. Evidence for a direct interaction between the ATF-2/c-Jun heterodimeric complex and EBNA2 was obtained by EMSA and coimmunoprecipitation experiments. Thus, our results suggest that EBNA2-induced transactivation via the ATF/CRE site occurs through a direct contact between EBNA2 and an ATF-2/c-Jun heterodimer. EBNA2-independent promoter activation via this site, on the other hand, is mediated by a heterodimeric complex between the ATF-1 and CREB-1 factors.

MeSH Terms
Activating Transcription Factor 1 Activating Transcription Factor 2 Cell Line Cyclic AMP Response Element-Binding Protein/genetics DNA-Binding Proteins Epstein-Barr Virus Nuclear Antigens/genetics Gene Expression Regulation, Viral Herpesvirus 4, Human/genetics Humans Oncogene Proteins, Viral/genetics Promoter Regions, Genetic/genetics Transcription Factors/genetics Viral Matrix Proteins/genetics
Chemicals
ATF2 protein, human Activating Transcription Factor 1 Activating Transcription Factor 2 Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins EBV-associated membrane antigen, Epstein-Barr virus Epstein-Barr Virus Nuclear Antigens Oncogene Proteins, Viral Transcription Factors Viral Matrix Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sjöblom A
Department of Clinical Chemistry and Transfusion Medicine, Göteborg University, Sahlgrenska University Hospital, Gothenburg, Sweden. anna.sjoblom@ss.gu.se
Yang W
Palmqvist L
Jansson A
Rymo L
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.2.1365-1376.1998
Email
anna.sjoblom@ss.gu.se
Published
1998-02-00
Pages
1365-76
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC124615
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.72.2.1365-1376.1998 PMC Full Text View journal details
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