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Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 625-634
Stable expression of Epstein-Barr virus BZLF-1-encoded ZEBRA
protein activates p53-dependent transcription in human Jurkat
T-lymphoblastoid cells
David H. Dreyfus,
Masayuki Nagasawa,
Colm A. Kelleher, and
Erwin W. Gelfand
From the Division of Basic Sciences, Department of Pediatrics,
National Jewish Medical and Research Center, Denver, CO.
Interaction between viral proteins and tumor suppressor p53 is a
common mechanism of viral pathogenesis. The Epstein-Barr virus (EBV)
BZLF-1 ORF-encoded ZEBRA protein (also denoted EB1, Z, Zta) binds to
p53 in vitro and has been associated with the altered transcription of
p53-regulated genes in B lymphocytes and epithelial cells. In this
work, Jurkat T-lymphoblastoid cells that express ZEBRA were
characterized by the use of transiently transfected p53 and p53
reporter genes. Stable expression of ZEBRA was associated with the
activation of p53-dependent transcription and increased p53 dependent
apoptotic cell death. In Jurkat cell lines, stably expressed ZEBRA
protein was apparently localized to the cell cytoplasm, in contrast to
the typical nuclear localization of this protein in other cell types.
Previous studies have suggested that EBV infection of T lymphocytes may
contribute to the malignant transformation of T cells and the increased
replication of human immunodeficiency virus. Our observations suggest a
mechanism through which ZEBRA protein expressed in human T lymphocytes
could alter T-cell proliferation and apoptosis during EBV infection.
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