The Epstein–Barr virus (EBV)-encoded latent membrane protein-1 (LMP1), a functional homologue of the tumor necrosis factor receptor family, substantially contributes to EBV’s oncogenic potential by activating nuclear factor-iB (NF-iB). miR-155 is an oncogenic miRNA critical for B-cell maturation and immunoglobulin production in response to antigen. We report that miR-155 expression is much higher in EBV-immortalized B cells than in EBV-negative B cells. LMP1, but not LMP2, up-regulated the expression of miR-155, when transfected in EBVnegative B cells. We analyzed two putative NF-iB binding sites in the miR-155 promoter; both sites recruited NF-iB complex, in nuclear extract from EBV-immortalized cells. The exogenous expression of LMP1, in EBV-negative background, is temporally correlated to induction of p65 with binding on both NF-iB sites and with miR-155 overexpression. The induction of p65 binding together with increased RNA polymerase II binding, confirms that LMP1- mediated activation of miR-155 occurs transcriptionally. In reporter assays, miR-155 promoter lacking NF-iB binding sites was no longer activated by LMP1 expression and an intact AP1 site is needed to attain maximum activation. Finally, we demonstrate that LMP1-mediated activation of miR-155 in an EBV-negative background correlates with reduction of protein PU.1, which is a possible miR target.

The Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through NF-κB pathway / G., Gatto; A., Rossi; D., Rossi; S., Kroening; S., Bonatti; Mallardo, Massimo. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - STAMPA. - 36:(2008), pp. 6608-6619. [10.1093/nar/gkn666]

The Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through NF-κB pathway

MALLARDO, MASSIMO
2008

Abstract

The Epstein–Barr virus (EBV)-encoded latent membrane protein-1 (LMP1), a functional homologue of the tumor necrosis factor receptor family, substantially contributes to EBV’s oncogenic potential by activating nuclear factor-iB (NF-iB). miR-155 is an oncogenic miRNA critical for B-cell maturation and immunoglobulin production in response to antigen. We report that miR-155 expression is much higher in EBV-immortalized B cells than in EBV-negative B cells. LMP1, but not LMP2, up-regulated the expression of miR-155, when transfected in EBVnegative B cells. We analyzed two putative NF-iB binding sites in the miR-155 promoter; both sites recruited NF-iB complex, in nuclear extract from EBV-immortalized cells. The exogenous expression of LMP1, in EBV-negative background, is temporally correlated to induction of p65 with binding on both NF-iB sites and with miR-155 overexpression. The induction of p65 binding together with increased RNA polymerase II binding, confirms that LMP1- mediated activation of miR-155 occurs transcriptionally. In reporter assays, miR-155 promoter lacking NF-iB binding sites was no longer activated by LMP1 expression and an intact AP1 site is needed to attain maximum activation. Finally, we demonstrate that LMP1-mediated activation of miR-155 in an EBV-negative background correlates with reduction of protein PU.1, which is a possible miR target.
2008
The Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through NF-κB pathway / G., Gatto; A., Rossi; D., Rossi; S., Kroening; S., Bonatti; Mallardo, Massimo. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - STAMPA. - 36:(2008), pp. 6608-6619. [10.1093/nar/gkn666]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/343379
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