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PMID: 11739688 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Epstein-Barr virus nuclear antigen 3C putative repression domain mediates coactivation of the LMP1 promoter with EBNA-2.

Journal of virology ·Vol. 76 ·No. 1 ·2002-01-00 ·Pages 232-42

Lin J, Johannsen E, Robertson E, Kieff E

Abstract

The Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) regulates virus and cell genes and is essential for EBV-mediated transformation of primary B lymphocytes. EBNA-3C associates with the cellular DNA sequence-specific transcription factors RBP-Jkappa and PU.1 and coactivates the EBV LMP1 promoter with EBNA-2 in BL2 and Raji cells under conditions of restrictive growth. We now find that EBNA-3C is similar to EBNA-LP in coactivating the LMP1 promoter with EBNA-2 in non-EBV-infected Burkitt lymphoma cells under conditions of maximal cell growth, whereas the EBV Cp promoter is repressed under the same conditions. EBNA-3A and EBNA-3B coactivation are at most 40% that of EBNA-3C. The RBP-Jkappa binding sites of EBNA-2 and the LMP1 promoter are not required for EBNA-3C coactivation, whereas the PU.1 site in the LMP1 promoter is required for EBNA-2-mediated activation and EBNA-3C coactivation. EBNA-3C amino acids (aa) 365 to 545, including most of the previously identified repression domain (M. Bain, R. J. Watson, P. J. Farrell, and M. J. Allday, J. Virol. 70:2481-2489, 1996), are necessary and sufficient for coactivation with wild-type EBNA-2. EBNA-3C can also coactivate with the EBNA-2 acidic activating domain; this activation does not require aa 343 to 545. These data indicate that there are at least two mechanisms by which EBNA-3C coactivates the LMP1 promoter with EBNA-2. Of the proteins that interact with EBNA-3C in a yeast two-hybrid screen, only the ubiquitin-like proteins SUMO-1 and SUMO-3/hSMT3B map to aa 365 to 545, implicating these molecules in EBNA-3C coactivation. In addition, SUMO-1 associates at a high level with EBNA-3C in lymphoblasts. Promoter coactivation by EBNA-3C is likely to be important in ensuring adequate levels of LMP1, while inhibition of the EBNA-Cp promoter under the same conditions prevents uncontrolled up-regulation of EBNA expression from a positive-feedback loop.

MeSH Terms
Antigens, Viral/genetics,metabolism,physiology B-Lymphocytes/virology Cell Line Cell Transformation, Viral Epstein-Barr Virus Nuclear Antigens/metabolism Humans Lymphocyte Activation Promoter Regions, Genetic Repressor Proteins/genetics,physiology Transcription, Genetic Viral Matrix Proteins/genetics,metabolism Viral Proteins
Chemicals
Antigens, Viral EBNA-2 protein, Human herpesvirus 4 EBNA-3C, epstein-barr virus EBV-associated membrane antigen, Epstein-Barr virus Epstein-Barr Virus Nuclear Antigens Repressor Proteins Viral Matrix Proteins Viral Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lin Jeffrey
Virology Program and Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Johannsen Eric
Robertson Erle
Kieff Elliott
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.1.232-242.2002
Published
2002-01-00
Pages
232-42
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC135708
Subset
IM
Grants
NCI NIH HHS · CA-47006 · United States
NCI NIH HHS · K12 CA077845 · United States
NCI NIH HHS · 5K12 CA77845-03 · United States
NCI NIH HHS · R01 CA047006 · United States
NCI NIH HHS · R35 CA047006 · United States
External Links
PubMed source DOI: 10.1128/jvi.76.1.232-242.2002 PMC Full Text View journal details
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