The level of c-fgr RNA is increased by EBNA-2, an Epstein-Barr virus gene required for B-cell immortalization

Knutson, Joyce C.

doi:10.1128/jvi.64.6.2530-2536.1990

Cited by 149 publications

(62 citation statements)

References 59 publications

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“…It is a transcriptional activator of viral and cellular genes and is essential for the transforming potential of the virus. EBNA2 modulates host cell gene expression by induction of cellular antigens CD21 and CD23 (Calender et al, 1987;Wang et al, 1987;Cordier et al, 1990) and the proto-oncogene c-fgr (Knutson et al, 1990). EBNA2 activates transcription of the genes of the three virally encoded membrane antigens (Abbot et al, 1990;Fahraeus et al, 1990;Zimber-Strobl et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2.

et al. 1995

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Infection of primary B‐lymphocytes by Epstein‐Barr virus (EBV) leads to growth transformation of these B‐cells in vitro. EBV nuclear antigen 2 (EBNA2), one of the first genes expressed after EBV infection of B‐cells, is a transcriptional activator of viral and cellular genes and is essential for the transforming potential of the virus. We generated conditional EBV mutants by expressing EBNA2 as chimeric fusion protein with the hormone binding domain of the estrogen receptor on the genetic background of the virus. Growth transformation of primary normal B‐cells by mutant virus resulted in estrogen‐dependent lymphoblastoid cell lines expressing the chimeric EBNA2 protein. In the absence of estrogen about half of the cells enter a quiescent non‐proliferative state whereas the others die by apoptosis. EBNA2 is thus required not only for initiation but also for maintenance of transformation. Growth arrest occurred at G1 and G2 stages of the cell cycle, indicating that functional EBNA2 is required at different restriction points of the cell cycle. Growth arrest is reversible for G1/G0 cells as indicated by the sequential accumulation and modification of cell cycle regulating proteins. EBV induces the same cell cycle regulating proteins as polyclonal stimuli in primary B‐cells. These data suggest that EBV is using a common pathway for B‐cell activation bypassing the requirement for antigen, T‐cell signals and growth factors.

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Section: Introductionmentioning

confidence: 99%

B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2.

et al. 1995

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“…It modulates the expression of the B cell activation markers CD21 and CD23 and the tyrosine kinase c-fgr (Calender et al, 1987;Wang,F. et al, 1987;Cordier et al, 1990; Knutson, 1990). In…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival.

Zimber-Strobl¹,

Kempkes²,

Marschall³

et al. 1996

The EMBO Journal

103

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Epstein‐Barr virus (EBV) infects human primary B lymphocytes and induces and maintains proliferation of these cells efficiently in vitro. Mutants of Epstein‐Barr virus which express EBV nuclear antigen 2 (EBNA2) in a conditional fashion allow dissection of individual contributions of viral genes to B cell immortalization. EBNA2 is a transcriptional activator of cellular and viral genes, including the viral latent membrane protein 1 (LMP1), which is essential for B cell immortalization and has oncogenic effects in non‐lymphoid cells. To analyze the role of this gene in B cell immortalization, LMP1 was constitutively expressed in B cells infected with EBV carrying a conditional EBNA2 allele. In the absence of functional EBNA2, LMP1 was incapable of sustaining B cell proliferation in two independent assays but induced a phenotype consistent with prolonged cell viability. Activation of CD40 displayed a comparable phenotype. These data indicate that both CD40 activation and LMP1 expression may use a common pathway for B cell activation. Proliferation of human B cells, however, requires one or more additional signals triggered by EBNA2.

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“…It appears in two allelic forms (EBNA2A and EBNA2B) in natural isolates which share -50% homology (Zimber et al, 1986). EBNA2, together with EBNA-LP, is the first viral gene expressed after infection of primary B cells, and is a transcriptional activator of latent viral as well as cellular genes (CD21, CD23 and c-fgr) (Calender et al, 1987;Wang et al, 1987;Abbot et al, 1990;Cordier et al, 1990;Fahraeus et al, 1990;Ghosh and Kieff, 1990;Knutson, 1990;Sung et al, 1991;Woisetschlaeger et al, 1991;Zimber-Strobl et al, 1991Jin and Speck, 1992;Ling et al, 1993;Laux et al, 1994a;Meitinger et al, 1994). EBNA2 has been shown to exert its transactivating function, at least in part, by binding to a ubiquitously expressed cellular protein, RBP-JK, which binds to DNA in a sequence-specific manner (Grossmann et al, 1994;Henkel et al, 1994;Waltzer et al, 1994;Zimber-Strobl et al, 1994), and through interaction with transcription factors of the ets gene family (Spi-1, PU-1) (Laux et al, 1994b;Johannsen et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus nuclear antigen 2 is a transcriptional suppressor of the immunoglobulin mu gene: implications for the expression of the translocated c-myc gene in Burkitt's lymphoma cells.

et al. 1996

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A conditional mutant of Epstein‐Barr virus nuclear antigen 2 (EBNA2) regulated by estrogen was employed to study the effect of EBNA2 on the cellular phenotype. Activation of EBNA2 in lymphoblastoid cell lines (LCLs) and in B cell lymphoma lines resulted in down‐regulation of cell surface IgM and Ig‐mu steady‐state RNA expression. In LCLs, activation of EBNA2 is required for maintaining proliferation, whereas in Burkitt's lymphoma (BL) cell lines with t(8;14) translocations, activation of EBNA2 induces growth arrest. In these cells, Northern and nuclear run‐on analyses revealed rapid simultaneous repression of Ig‐mu and c‐myc transcription as early as 30 min after activation of EBNA2. Since c‐myc expression is under the control of the Ig heavy chain locus in BL cell lines with a t(8;14) translocation, we propose that Ig‐mu and c‐myc are down‐regulated by EBNA2 through a common mechanism.

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The level of c-fgr RNA is increased by EBNA-2, an Epstein-Barr virus gene required for B-cell immortalization

Cited by 149 publications

References 59 publications

B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2.

B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2.

Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival.

Epstein-Barr virus nuclear antigen 2 is a transcriptional suppressor of the immunoglobulin mu gene: implications for the expression of the translocated c-myc gene in Burkitt's lymphoma cells.

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