title: Latent membrane protein 1 of Epstein-Barr virus coordinately regulates proliferation with control of apoptosis.
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 G1/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.
authors.affiliation: Department of Gene Vectors, GSF-National Research Center for Environment and Health, Marchioninistr. 25, Munich D-81377, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Dirmeier
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Ellen
authors.initials: E
authors.lastname: Kilger
authors.forename: Ute
authors.initials: U
authors.lastname: Schultheiss
authors.forename: Cinthia
authors.initials: C
authors.lastname: Briseño
authors.forename: Olivier
authors.initials: O
authors.lastname: Gires
authors.forename: Arnd
authors.initials: A
authors.lastname: Kieser
authors.forename: Dirk
authors.initials: D
authors.lastname: Eick
authors.forename: Bill
authors.initials: B
authors.lastname: Sugden
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hammerschmidt
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D016193:G1 Phase; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D020411:Oligonucleotide Array Sequence Analysis; D016196:S Phase; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000502:physiology*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins