EBV Conference 2008 Guangzhou - Baylor College of Medicine

123 (RegID: 1118)
Surya Pavan Yenamandra
Institution: MTC (department of Microbiology, Tumor and Cell Biology), Karolinska Institute
e-mail: suryen@ki.se
EPSTEIN-BARR VIRUS ENCODED EBNA3 BINDS TO VITAMIN D RECEPTOR AND
REPRESSES ITS TRANSACTIVATION FUNCTION
Surya Pavan Yenamandra1, Ulf Hellman3, Bettina Kempkes4, Sabine Petermann4, Tom Sculley5, George
Klein1 and Elena Kashuba1
Posterabstract:
EBV is one of the most highly transforming viruses known. The EBV-immortalized lymphoblastoid cell
lines (LCLs) express six nuclear proteins (EBNAs) and three membrane proteins (LMPs), out of which
five, EBNA-2, -3, -5, -6 and LMP1 are essential for transformation. The mechanism of transformation is
not well understood, but it is clear that the virus exploits the normal signaling pathways of the B
lymphocyte. We have discovered and published the seven previously unknown interactions between
three transforming nuclear proteins, EBNA-3, EBNA-5 and EBNA-6 and cellular proteins, using the yeast
two-hybrid system, GST-pull down assay and surface plasmon resonance (SPR).
Currently, we found 5 novel cellular binding partners of EBNA3 protein (DNA Helicase II, SWI/SNF1
chromatin remodeling complex, H2A, H2B, Heterogeneous Nuclear Ribonucleoprotein AB isoform A),
based on immunoprecipitation studies and mass spectrometry. This study was done on various deletion
mutants of EBNA3 protein (GFP fused at N-terminal region of EBNA3 mutants).
It is known that SWI/SNF1 (one of novel cellular binding partner) cooperates with VDR complex and
regulates various responsive genes of VDR (Vitamin D receptor). We performed immunoprecipitation
studies and showed that EBNA3 is one of the units of VDR protein complex. Moreover, using Real
Time PCR, we showed that EBNA3 represses the expression of VDR responsive genes. This study was
done by relatively comparing LCLs and EBNA3 negative LCLs. Upon the treatment with Vitamin D3
(VDR ligand) we observed similar repressive activity of EBNA3 on VDR responsive genes. In conclusion,
we showed that EBNA3 interacts with VDR complex and represses its transactivation function.
EBV Conference 2008 Guangzhou
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