Ubiquitination of MDM2 modulated by Epstein-Barr virus encoded latent membrane protein 1

Epstein-Barr virus encoded latent membrane protein 1 (LMP1), an oncogenic protein, plays an important role in the carcinogenesis of nasopharyngeal carcinoma. The MDM2 gene is a cellular pro-oncogene that is abnormally up-regulated in human tumors. MDM2 is overexpressed in nasopharyngeal carcinoma, which is associated with the presence of EBV and cervical lymph node metastasis. Because MDM2 is capable of self-ubiquitination, and the ubiquitin proteasome pathway-dependent degradation is an important mechanism for regulating MDM2 levels in cells. Here we show that LMP1 augment MDM2 protein expression in dose-dependent level, and also lead to a drastic accumulation of ubiquitinated MDM2,species, this effect is associated with the stability of MDM2 modulated by LMP1. This is the first time to explain LMP1-regulated MDM2 through a post-ubiquitination mechanism. (c) 2007 Elsevier B.V. All rights reserved.