EBV Conference 2008 Guangzhou - Baylor College of Medicine

124 (RegID: 1119; 1120)
Ya Cao
Institution: Cancer Research Insitute, Xiangya School of Medicine, Central South University
e-mail: ycao98@public.cs.hn.cn
EPSTEIN-BARR VIRUS ENCODED LATENT MEMBRANE PROTEIN 1 MEDIATED
SIGNALING TRANSDUCTION PATHWAY IN NASOPHARYNGEAL CARCINOMA
Ya Cao
Posterabstract:
Latent membrane protein 1(LMP1) is considered as oncogene among Epstein-Barr virus (EBV) encoded
proteins. C terminal-region of LMP1 is the key functional domain which could trigger multiple signaling
transduction cascades to alter cell growth and survival. Combined the novel strategy of phosphor-protein
enrichment with proteomics technology, also called “signalomics”, twenty-five signaling molecules
triggered by LMP1 in nasopharyngeal carcinoma (NPC) were identified. These new signaling molecules
or targets show some unknown function in LMP1 mediated signaling pathways. According to the existent
signaling pathway previously and these new targets, we constructed the whole signaling network triggered
by LMP1 for the first time in NPC.
Based on the signaling transduction network mediated by LMP1, we systemic confirmed multiple kinase
signaling pathways activated by LMP1, such as PI-PLC/PKC、MAPK、JAK/STAT and PI3K/AKT
signaling pathways. These activated kinases could phosphorylate some important signaling molecules in
network, including STAT3, Annexin A2, p53, EGFR, stathmin and survivin, which promoted cell
malignant proliferation and the inhibition of apoptosis. Besides these “old”, “nodel” molecules embedded
with new function in network, some new proteins in LMP1 mediated signaling transduction network have
been identified in success, such as Annexin A2 and stathmin. Our data showed that LMP1 increased the
serine phosphorylation of Annexin A2 by activating the PI-PLC-PKCα/PKCβ pathway, especially by
PKCβ pathway. And serine 25 phosphorylation of annexin A2 was associated with the nuclear entry of
annexin A2 and cell proliferation. LMP1 could regulate the phosphorylation of stathmin through cdc2 and
MAPK signaling pathway with cell-cycle phase. So there should be more new proteins and their new
function need to be confirmed to enrich the LMP1 mediated signaling network. These findings provide us
with a novel view of comprehensive understanding the function of LMP1 from the signaling transduction
in the carcinogenesis of NPC.
EBV Conference 2008 Guangzhou
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