Sustained expression of the novel EBV-induced zinc finger gene, ZNFEB, is critical for the transition of B lymphocyte activation to oncogenic growth transformation. |
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Authors: | Cathryn E Tune Marc Pilon Yuriko Saiki H-Michael Dosch |
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Affiliation: | Division of Infection, Immunity, Injury, and Repair, The Hospital for Sick Children, Toronto, Ontario, Canada. |
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Abstract: | EBV is a human tumor virus that infects and establishes latency in the majority of humans worldwide. In vitro, EBV growth transforms primary B lymphocytes into lymphoblastoid cell lines with high efficiency. We have used cDNA subtraction cloning to identify cellular target genes required for growth transformation and identified a new C(2)H(2) (Krüppel-type) zinc finger gene, ZNF(EB), that is trans-activated early following EBV infection. In this study, we characterize ZNF(EB), including its intronless locus, and human and mouse protein variants. The gene is transiently expressed during normal lymphocyte activation, and its expression is sustained in EBV-positive but not EBV-negative B cell lines. There is limited expression in nonhemopoietic tissues. Its critical role in the growth transformation of B lineage cells is indicated by the abrogation of transformation with antisense strategies. ZNF(EB) maps to chromosome 18q12, a region with mutations in numerous, predominantly hemopoietic malignancies. |
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