EBV-encoded EBNA-6 binds and targets MRS18-2 to the nucleus, resulting in the disruption of pRb-E2F1 complexes

Elena Kashuba, Mariya Yurchenko, Surya Pavan Yenamandra, Boris Snopok, Maria Isaguliants, Laszlo Szekely, George Klein

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Epstein-Barr virus (EBV), like other DNA tumor viruses, induces an S-phase in the natural host cell, the human B lymphocyte. This is linked with blast transformation. It is believed that the EBV-encoded nuclear antigen 6 (EBNA-6) is involved in the regulation of cell cycle entry. However, the possible mechanism of this regulation is not approached. In our current study, we found that EBNA-6 binds to a MRPS18-2 protein, and targets it to the nucleus. We found that MRPS18-2 binds to both hypo- and hyperphosphorylated forms of Rb protein specifically. This binding targets the small pocket of pRb, which is a site of interaction with E2F1. The MRPS18-2 competes with the binding of E2F1 to pRb, thereby raising the level of free E2F1. Our experimental data suggest that EBNA-6 may play a major role in the entry of EBV infected B cells into the S phase by binding to and raising the level of nuclear MRPS18-2, protein. This would inhibit pRb binding to E2F1 competitively and lift the block preventing S-phase entry.

Original languageEnglish
Pages (from-to)5489-5494
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number14
DOIs
StatePublished - 8 Apr 2008
Externally publishedYes

Keywords

  • Cell cycle
  • Cell transformation
  • S-phase entry
  • Surface plasmon resonance

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