The Epstein–Barr virus (EBV)-encoded latent membrane protein-1 (LMP1), a functional homologue of the tumor necrosis factor receptor family, substan15 tially 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 20 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 25 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 30 induction of p65 binding together with increased RNA polymerase II binding, confirms that LMP1mediated activation of miR-155 occurs transcriptionally. In reporter assays, miR-155 promoter lacking NF-iB binding sites was no longer activated 35 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 40 miR target.

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

Epstein–Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kB pathway

BONATTI, STEFANO;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, substan15 tially 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 20 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 25 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 30 induction of p65 binding together with increased RNA polymerase II binding, confirms that LMP1mediated activation of miR-155 occurs transcriptionally. In reporter assays, miR-155 promoter lacking NF-iB binding sites was no longer activated 35 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 40 miR target.
2008
Epstein–Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kB pathway / Gatto, G.; Rossi, A.; Rossi, D.; Kroening, S.; Bonatti, Stefano; 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/11588/341012
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