EBV Conference 2008 Guangzhou - Baylor College of Medicine

125 (RegID: 1121)
Lili Li
Institution: Cancer Research Institute, Xiangya School of Medicine, Central South University
e-mail: Blue.leelily@gmail.com
THE FUNCTIONAL ACTIVATION OF P53 REGULATED BY EPSTEIN-BARR VIRUS
ENCODED BY LATENE MEMBRANE PROTEIN 1
Lili Li
Posterabstract:
EBV encoded latent memebrane protein 1 (LMP1), an oncogenic protein, plays an important role in the
carcinogenesis of nasopharyngeal carcinoma (NPC). Unlike most human tumors, nearly 100% are
wild-type p53 in NPC. P53 accumulation is significantly correlated to LMP1 in NPC biopsies. However
the molecular mechanisms leading to the stabilization and functional activation of p53 mediated by LMP1
have not been completely elucidated. Here, we present the first evidence that LMP1 could promote wt-p53
nuclear accumulation, up-regulate transcriptional activity and protein expression of p53. Interestingly, p53
can be activated and phosphorylated clearly at Ser15, Ser20, Ser392 and Thr81 mediated by LMP1. MAP
kinases play a critical role in LMP1-induced phosphorylation of p53 at multiple sites, and JNK signaling
pathway mediated p53 Ser 20 phosphorylation is more important than others. Furthermore, the
phosphorylation of p53 enhanced the expression of p21, MDM2. Interestingly, we found that LMP1
decreased the binding of MDM2 to p53, so it suggested that LMP1 could regulate p53 function via
ubiquitination, moreover the ubiquitination of p53 regulated by LMP1 is phosphorylation depended.
When inhibited p53, resistance to apoptosis was observed. Taken together, these results suggest that
accumulated p53, as an important transcriptional factor, play a key role in maintaining EBV latent
infection, promote cell transformation and regulate of cell cycle in the carcinogenesis of NPC.
EBV Conference 2008 Guangzhou
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