Li Lili, Li Zijian, Zhou Shanghui, Xiao Lanbo, Guo Lili, Tao Yongguang, Tang Min, Shi Ying, Li Wei, Yi Wei, Cao Ya
Cancer Research Institute, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan, PR China.
Virus Res. 2007 Dec;130(1-2):275-80. doi: 10.1016/j.virusres.2007.05.013. Epub 2007 Jun 18.
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.
爱泼斯坦-巴尔病毒编码的潜伏膜蛋白1（LMP1）是一种致癌蛋白，在鼻咽癌的致癌过程中起重要作用。MDM2基因是一种细胞原癌基因，在人类肿瘤中异常上调。MDM2在鼻咽癌中过度表达，这与EBV的存在和颈部淋巴结转移有关。由于MDM2能够自我泛素化，且泛素蛋白酶体途径依赖性降解是调节细胞中MDM2水平的重要机制。在这里，我们表明LMP1以剂量依赖的水平增加MDM2蛋白表达，并且还导致泛素化MDM2物种的急剧积累，这种效应与LMP1调节的MDM2的稳定性有关。这是首次通过泛素化后机制解释LMP1对MDM2的调节。
