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.
Li
Lili
L
Cancer Research Institute, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan, PR China.
Li
Zijian
Z
Zhou
Shanghui
S
Xiao
Lanbo
L
Guo
Lili
L
Tao
Yongguang
Y
Tang
Min
M
Shi
Ying
Y
Li
Wei
W
Yi
Wei
W
Cao
Ya
Y
D002460:Cell Line; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2