Epstein-Barr virus EBNA2 blocks Nur77-mediated apoptosis

Jae Myun Lee, Kyoung Ho Lee, Magdalena Weidner, Barbara A. Osborne, S. Diane Hayward

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)11878-11883
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number18
DOIs
StatePublished - Sep 3 2002

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Sindbis Virus
Human Herpesvirus 4
Apoptosis
B-Lymphocytes
Cell Death
Epstein-Barr Virus Infections
Trans-Activators
Mitochondria
Viruses
Amino Acids

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Epstein-Barr virus EBNA2 blocks Nur77-mediated apoptosis. / Lee, Jae Myun; Lee, Kyoung Ho; Weidner, Magdalena; Osborne, Barbara A.; Hayward, S. Diane.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 18, 03.09.2002, p. 11878-11883.

Research output: Contribution to journalArticle

Lee, Jae Myun ; Lee, Kyoung Ho ; Weidner, Magdalena ; Osborne, Barbara A. ; Hayward, S. Diane. / Epstein-Barr virus EBNA2 blocks Nur77-mediated apoptosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 18. pp. 11878-11883.
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