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PMID: 12195020 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Epstein-Barr virus EBNA2 blocks Nur77- mediated apoptosis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 18 ·2002-09-03 ·Pages 11878-83

Lee JM, Lee KH, Weidner M, Osborne BA, Hayward SD

Abstract

Epstein-Barr virus infection in vitro immortalizes primary B cells. EBNA2 is an Epstein-Barr virus-encoded transcriptional transactivator that mimics the effects of activated Notch signaling and is essential for this proliferative response. An assay using Sindbis virus (SV) as a cell death inducer revealed that, like Notch, EBNA2 also has antiapoptotic activity. We show that Nur77 is a mediator of SV-induced cell death and that EBNA2 antiapoptotic activity results from interaction with Nur77. EBNA2 colocalized with Nur77 in transfected cells and coprecipitated with Nur77 in IB4 B cells. EBNA2 binds to Nur77 through sequences in the EBNA2 amino acid 123-147 conserved domain and an EBNA2 mutant unable to bind Nur77 also lost the ability to protect cells from SV-induced apoptosis. EBNA2 exerted its antideath function by retaining Nur77 in the nucleus and preventing Nur77 from targeting mitochondria in response to apoptotic stimuli. Thus, targeting of Nur77 can be added to the list of strategies used by viruses to counter apoptosis.

MeSH Terms
Animals Apoptosis/physiology Cell Line Cell Nucleus/metabolism Cricetinae DNA-Binding Proteins/metabolism,physiology Epstein-Barr Virus Nuclear Antigens/physiology Fluorescent Antibody Technique Herpesvirus 4, Human/physiology Membrane Proteins/metabolism Mice Nuclear Receptor Subfamily 4, Group A, Member 1 Precipitin Tests Protein Transport Receptor, Notch1 Receptors, Cell Surface Receptors, Cytoplasmic and Nuclear Receptors, Steroid Transcription Factors/metabolism,physiology Viral Proteins
Chemicals
DNA-Binding Proteins EBNA-2 protein, Human herpesvirus 4 Epstein-Barr Virus Nuclear Antigens Membrane Proteins NR4A1 protein, human Notch1 protein, mouse Nr4a1 protein, mouse Nuclear Receptor Subfamily 4, Group A, Member 1 Receptor, Notch1 Receptors, Cell Surface Receptors, Cytoplasmic and Nuclear Receptors, Steroid Transcription Factors Viral Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lee Jae Myun
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA.
Lee Kyoung-Ho
Weidner Magdalena
Osborne Barbara A
Hayward S Diane
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.182552499
Published
2002-09-03
Epub
2002-00-23
Pages
11878-83
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC129362
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007445 · United States
PHS HHS · R01 A47922 · United States
NIGMS NIH HHS · 5 T32 GM07445 · United States
NCI NIH HHS · R01 CA042245 · United States
NCI NIH HHS · R01 CA42245 · United States
External Links
PubMed source DOI: 10.1073/pnas.182552499 PMC Full Text View journal details
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