Bortezomib induction of C/EBPβ mediates Epstein-Barr virus lytic activation in Burkitt lymphoma

Courtney M. Shirley, Jianmeng Chen, Meir Shamay, Huili Li, Cynthia Zahnow, S. Diane Hayward, Richard F Ambinder

Research output: Contribution to journalArticle

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 proteinβ (C/EBPβ) in a variety of tumor cell lines. C/EBPβ 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/EBPβ 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/EBPβ knock-down. Therefore, C/EBPβ mediates the activation of EBV lytic gene expression associated with bortezomib and another UPR inducer.

Original languageEnglish (US)
Pages (from-to)6297-6303
Number of pages7
JournalBlood
Volume117
Issue number23
DOIs
StatePublished - Jun 9 2011

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CCAAT-Enhancer-Binding Proteins
Virus Activation
Burkitt Lymphoma
Human Herpesvirus 4
Viruses
Chemical activation
Gene expression
Unfolded Protein Response
Gene Expression
Thapsigargin
Switch Genes
Proteins
Proteasome Inhibitors
Proteasome Endopeptidase Complex
Bortezomib
Tumor Cell Line
Tumors
Genes
Binding Sites
Cells

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Bortezomib induction of C/EBPβ mediates Epstein-Barr virus lytic activation in Burkitt lymphoma. / Shirley, Courtney M.; Chen, Jianmeng; Shamay, Meir; Li, Huili; Zahnow, Cynthia; Hayward, S. Diane; Ambinder, Richard F.

In: Blood, Vol. 117, No. 23, 09.06.2011, p. 6297-6303.

Research output: Contribution to journalArticle

Shirley, Courtney M. ; Chen, Jianmeng ; Shamay, Meir ; Li, Huili ; Zahnow, Cynthia ; Hayward, S. Diane ; Ambinder, Richard F. / Bortezomib induction of C/EBPβ mediates Epstein-Barr virus lytic activation in Burkitt lymphoma. In: Blood. 2011 ; Vol. 117, No. 23. pp. 6297-6303.
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