Epstein-Barr virus (EBV) has been causally associated with at least five human malignancies. The exact contributions made by EBV to these cancers remain unknown. We demonstrate that one viral protein found in all EBV-associated malignancies, Epstein-Barr nuclear antigen 1 (EBNA-1), is required for survival of one of these cancers, EBV-positive Burkitt's lymphoma. Inhibition of EBNA-1 decreases survival of these tumor cells by inducing apoptosis. Expression of EBNA-1 in uninfected cells also can inhibit apoptosis induced by expression of p53 in the absence of the EBV genome. Our findings demonstrate that EBNA-1 is critical for the continued survival of EBV-associated Burkitt's lymphoma, and, by extension, for the other B cell tumors with which EBV is associated. Efficient inhibitors of EBNA-1's functions would likely prove useful in the therapy of EBV-associated malignancies.
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Maternidade Dr Alfredo da Costa, Dept Maternal Fetal Med, Lisbon, PortugalMaternidade Dr Alfredo da Costa, Dept Maternal Fetal Med, Lisbon, Portugal
Cordeiro, Alexandra
Machado, A. I.
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Maternidade Dr Alfredo da Costa, Dept Maternal Fetal Med, Lisbon, PortugalMaternidade Dr Alfredo da Costa, Dept Maternal Fetal Med, Lisbon, Portugal
Machado, A. I.
Borges, A.
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Maternidade Dr Alfredo da Costa, Dept Internal Med, Lisbon, PortugalMaternidade Dr Alfredo da Costa, Dept Maternal Fetal Med, Lisbon, Portugal
Borges, A.
Alves, M. J.
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Maternidade Dr Alfredo da Costa, Dept Maternal Fetal Med, Lisbon, PortugalMaternidade Dr Alfredo da Costa, Dept Maternal Fetal Med, Lisbon, Portugal
Alves, M. J.
Frade, M. J.
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Portuguese Inst Oncol, Dept Hematol, Lisbon, PortugalMaternidade Dr Alfredo da Costa, Dept Maternal Fetal Med, Lisbon, Portugal
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Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, EnglandUniv Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
Traylen, Chris
Ramasubramanyan, Sharada
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Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, EnglandUniv Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
Ramasubramanyan, Sharada
Zuo, Jianmin
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Univ Birmingham, Coll Med & Dent Sci, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England
Univ Birmingham, Coll Med & Dent Sci, Ctr Human Virol, Birmingham B15 2TT, W Midlands, EnglandUniv Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
Zuo, Jianmin
Rowe, Martin
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Univ Birmingham, Coll Med & Dent Sci, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England
Univ Birmingham, Coll Med & Dent Sci, Ctr Human Virol, Birmingham B15 2TT, W Midlands, EnglandUniv Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
Rowe, Martin
Almohammad, Rajaei
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Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, EnglandUniv Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
Almohammad, Rajaei
Heesom, Kate
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Univ Bristol, Prote Facil, Bristol BS8 1TD, Avon, EnglandUniv Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
Heesom, Kate
Sweet, Steve M. M.
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Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, EnglandUniv Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
Sweet, Steve M. M.
Matthews, David A.
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Univ Bristol, Sch Cellular & Mol Med, Bristol BS8 1TD, Avon, EnglandUniv Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
Matthews, David A.
Sinclair, Alison J.
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Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, EnglandUniv Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England