Latent membrane protein 1 of Epstein-Barr virus regulates p53 phosphorylation through MAP kinases.

ABSTRACT

The Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1), an oncogenic protein, plays an important role in the carcinogenesis of nasopharyngeal carcinoma (NPC). Phosphorylation of p53 protein is likely to play the key role in regulating its activity. p53 protein accumulates but mutation of p53 gene is not common in NPC. The molecular mechanisms of p53 augmentation have not been completely elucidated. Here, the role of MAP kinases in the phosphorylation of p53 modulated by LMP1 was determined. p53 could be activated and phosphorylated clearly at Ser15, Ser20, Ser392, and Thr81 modulated by LMP1. Furthermore, LMP1-induced phosphorylation of p53 at Ser15 was directly by ERKs; at Ser20 and Thr81 by JNK, at Ser 15 and Ser392 by p38 kinase. The phosphorylation of p53 was associated with its transcriptional activity and stability modulated by LMP1. These results strongly suggest that MAP kinases have a direct role in LMP1-induced phosphorylation of p53 at multiple sites, which provide a novel view for us to understand the mechanism of the activation of p53 in the carcinogenesis of nasopharyngeal carcinoma.