Latent membrane protein 1 of Epstein-Barr virus coordinately regulates proliferation with control of apoptosis

Ulrike Dirmeier, Reinhard Hoffmann, Ellen Kilger, Ute Schultheiss, Cinthia Briseño, Olivier Gires, Arnd Kieser, Dirk Eick, Bill Sugden, Wolfgang Hammerschmidt

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

Latent membrane protein 1 (LMP1), an oncoprotein encoded by Epstein-Barr virus (EBV), is an integral membrane protein, which acts like a constitutively active receptor. LMP1 is critical for some facet of EBV's induction and maintenance of proliferation of infected B cells. It, in part, mimics signaling by the CD40 receptor and has been implicated in regulating proliferation, survival, or both properties of EBV-infected cells. We established a conditional LMP1 allele in the context of the intact EBV genome to define the immediate-early cellular target genes regulated by LMP1 in order to assess its contributions to infected human B cells. The functional analysis of this conditional system indicated that LMP1 specifically induces mitogenic B-cell activation through c-myc and Jun/AP1 family members and confirms its direct role in upregulating expression of multiple genes with opposing activities involved in cell survival. LMP1's signals were found to be essential for the G 1/S transition in human B cells; cells lacking LMP1's signals are cell cycle arrested and survive quiescently. LMP1's activities are therefore not required to maintain survival in nonproliferating cells. LMP1 does induce both pro- and antiapoptotic genes whose balance seems to permit survival during LMP1's induction and maintenance of proliferation.

Original languageEnglish
Pages (from-to)1711-1717
Number of pages7
JournalOncogene
Volume24
Issue number10
DOIs
StatePublished - 3 Mar 2005

Keywords

  • B cell proliferation
  • Epstein-Barr virus
  • Latent membrane protein
  • Target genes
  • c-myc
  • p53

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