EBV Conference 2008 Guangzhou - Baylor College of Medicine

63 (RegID: 1236)
Junying Jia
Institution: University of Birmingham
e-mail: j.jia@bham.ac.uk
IDENTIFICATION OF DELTANP63 AS A MODULATOR OF LMP1 EXPRESSION IN
EBV-INFECTED EPITHELIAL CELLS
J.Jia, C.W. Dawson and L.S.Young
Posterabstract:
Epstein–Barr virus (EBV) is a ubiquitous human herpesvirus implicated in the development of both
lymphoid and epithelial tumors. Whereas expression of the LMP1 protein is variable in NPC, LMP2A is
more frequently expressed. Previous studies from our group have shown that epithelial cell lines infected
with an LMP2A-deleted EBV (LMP2A-rEBV) express low levels of LMP1, suggesting that LMP2A
negatively regulates LMP1 expression in epithelial cells (Stewart, 2004). We now show that LMP1 is
subject to regulation by the p53 transcription factor family member deltaNp63, and that LMP2A regulates
LMP1 expression by targeting deltaNp63 for degradation.
In this study we show that LMP1 protein is elevated in LMP2A-rEBV infected carcinoma cells expressing
high levels of endogenous deltaNp63. Moreover, exogenous expression of deltaNp63 could further
increase LMP1 promoter activity and protein expression, whereas silencing deltaNp63 by RNAi reduced
LMP1 promoter activity and decreased LMP1 protein.
A role for LMP2A in this process was established, as transient expression of LMP2A into
deltaNp63-positive carcinoma cells stably infected with LMP2A-rEBV, resulted in a marked reduction in
deltaNp63 expression and a corresponding decrease in LMP1 protein. ChIP assay confirmed that
deltaNp63 bound to a region located upstream of the L1-TR LMP1 promoter. This study identifies
deltaNp63 as a key effector molecule in modulating the expression of LMP1 in EBV-infected epithelial
cells.
EBV Conference 2008 Guangzhou
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