EBV Conference 2008 Guangzhou - Baylor College of Medicine

149 (RegID: 1874; 1875)
Seiji Maruo
Institution: Hokkaido University
e-mail: smaruo@igm.hokudai.ac.jp
EBNA3C TRANSCRIPTIONAL REGULATION THROUGH RBP-JKAPPA IS CRITICAL FOR
GROWTH MAINTENANCE OF LYMPHOBLASTOID CELLS
Seiji Maruo 1, Yi Wu 1, Teru Kanda 1, Elliott Kieff 2, and Kenzo Takada 1, 1 Institute for Genetic
Medicine, Hokkaido University, 2 Brigham and Women’s Hospital, Harvard Medical School
Posterabstract:
Although EBNA3C is essential for EBV-induced primary B cell outgrowth into lymphoblastoid cell lines
(LCLs), the precise mechanisms by which EBNA3C contributes to LCL growth are still unclear. We
evaluated the ability of EBNA3C mutants to support the maintenance of LCL growth and found that an
EBNA3C mutant lacking aa 180 to 231, which was defective in RBP-Jkappa association, was unable to
support LCL growth maintenance. Moreover, analyses using a series of EBNA3C point mutants in which
alanine substitution mutations were introduced within aa 180 to 231 revealed that the ability of EBNA3C
point mutant to regulate transcription through RBP-Jkappa was well correlated with its ability to sustain
LCL growth maintenance. The data indicates that EBNA3C regulation of transcription through
RBP-Jkappa is critical for maintaining LCL growth.
We also examined the specific roles of p16INK4A and p14ARF in the growth arrest of LCLs induced by
EBNA3C inactivation. Inactivation of EBNA3C in LCLs resulted in transcriptional induction of
p16INK4A and p14ARF, which was accompanied by growth arrest of the LCLs. Transfection of plasmids
containing shRNAs targeting p16INK4A and p14ARF rescued the LCLs from the growth arrest. Thus,
p16INK4A and p14ARF repression may be a critical EBNA3C function.
EBV Conference 2008 Guangzhou
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