Bortezomib induction of C/EBPß mediates Epstein-Barr virus lytic activation in Burkitt lymphoma.
Blood
; 117(23): 6297-303, 2011 Jun 09.
Article
em En
| MEDLINE
| ID: mdl-21447826
ABSTRACT
Epstein-Barr virus (EBV) is associated with a variety of lymphoid malignancies. Bortezomib activates EBV lytic gene expression. Bortezomib, a proteasome inhibitor, leads to increased levels of CCAAT/enhancer-binding proteinß (C/EBPß) in a variety of tumor cell lines. C/EBPß activates the promoter of the EBV lytic switch gene ZTA. Bortezomib treatment leads to increased binding of C/EBP to previously recognized binding sites in the ZTA promoter. Knockdown of C/EBPß inhibits bortezomib activation of EBV lytic gene expression. Bortezomib also induces the unfolded protein response (UPR), as evidenced by increases in ATF4, CHOP10, and XBP1s and cleavage of ATF6. Thapsigargin, an inducer of the UPR that does not interfere with proteasome function, also induces EBV lytic gene expression. The effects of thapsigargin on EBV lytic gene expression are also inhibited by C/EBPß knock-down. Therefore, C/EBPß mediates the activation of EBV lytic gene expression associated with bortezomib and another UPR inducer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazinas
/
Ativação Viral
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Ácidos Borônicos
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Regulação Neoplásica da Expressão Gênica
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Regulação Viral da Expressão Gênica
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Linfoma de Burkitt
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Herpesvirus Humano 4
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Elementos de Resposta
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Proteína beta Intensificadora de Ligação a CCAAT
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos