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PMID: 9261383 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Epstein-Barr virus nuclear protein LP stimulates EBNA-2 acidic domain-mediated transcriptional activation.

Journal of virology ·Vol. 71 ·No. 9 ·1997-09-00 ·Pages 6611-8

Harada S, Kieff E

Abstract

Epstein-Barr virus (EBV) nuclear proteins EBNA-LP and EBNA-2 are the first two proteins expressed in latent infection of primary B lymphocytes. EBNA-2 is essential for lymphocyte transformation, and EBNA-LP is at least critical. While EBNA-2 activates specific viral and cellular promoters, EBNA-LP's role has been obscure. We now show that EBNA-LP stimulates EBNA-2 activation of the LMP1 promoter and of the LMP1/LMP2B bidirectional transcriptional regulatory element. EBNA-LP alone has only a negative effect. EBNA-LP also stimulates EBNA-2 activation of a multimerized regulatory element from the BamC EBNA promoter. Since both viral regulatory elements can bind the EBNA-2-associated cell protein RBPJ kappa, consensus RBPJ kappa binding sites were positioned upstream of the herpes simplex virus type 1 thymidine kinase promoter and were found to be sufficient for EBNA-LP and EBNA-2 coactivation. EBNA-LP strongly stimulated activation of an adenovirus E1b promoter with upstream Gal4 binding sites by a Gal4 DNA binding domain/ EBNA-2 acidic domain fusion protein, indicating that EBNA-LP coactivation requires only the EBNA-2 acidic domain to be localized near a promoter. The EBNA-LP stimulatory activity resides in the amino-terminal 66-amino-acid repeat domain. The carboxyl-terminal unique 45 amino acids appear to regulate EBNA-LP's effects. The first 11 amino acids of the 45 have a strong negative effect, while the last 10 are critical for the ability of the last 34 to relieve the negative effect. These results indicate that EBNA-LP's critical role in EBV-mediated cell growth transformation is in stimulating (and probably regulating) EBNA-2-mediated transcriptional activation.

MeSH Terms
Binding Sites DNA-Binding Proteins/genetics,metabolism Epstein-Barr Virus Nuclear Antigens/genetics,metabolism Gene Expression Regulation, Viral Herpesvirus 4, Human/genetics,metabolism Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein Nuclear Proteins Repetitive Sequences, Nucleic Acid Transcriptional Activation Transfection Tumor Cells, Cultured Viral Matrix Proteins/genetics
Chemicals
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 Viral Matrix Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Harada S
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Kieff E
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.71.9.6611-6618.1997
Published
1997-09-00
Pages
6611-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC191939
Subset
IM
Grants
NCI NIH HHS · CA47006 · United States
External Links
PubMed source DOI: 10.1128/JVI.71.9.6611-6618.1997 PMC Full Text View journal details
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