Interaction of Tumor Necrosis Factor Receptor-associated Factors with the Latent Membrane Protein 1 Is Essential for Activation of NF-κB
- VernacularTitle:EB病毒潜伏膜蛋白1通过结合TRAFs调控NF-κB
- Author:
Chengxing WANG
;
Xiaoyan LI
;
Huanhua GU
;
Xiyun DENG
;
Ya CAO
- Publication Type:Journal Article
- Keywords:
nasopharyngeal carcinoma;
latent membrane protein 1;
tumor necrosis factor receptor associated factors;
NF-κB
- From:
Progress in Biochemistry and Biophysics
2001;28(2):240-245
- CountryChina
- Language:Chinese
-
Abstract:
The Epstein-Barr virus latent membrane protein 1 (LMP1) oncopro tein causes multiple cellular changes, including activation of the NF-κB trans cription factor. To elucidate its possible mechanism, the interaction between LM P1 and the tumor necrosis factor receptor associated factor (TRAF) molecules was detected by the immunoprecipitation-Western blotting assay. Results showed tha t LMP1 was co-precipitated with TRAF1,2,3 in the LMP1-HNE2 cell line. In the m eantime, κB reporter gene analysis revealed that over expression of TRAF1 or TR AF2 augmented LMP1-mediated NF-κB activation from LMP1, suprisingly, overexpr ession of either TRAF3 or an dominant negative TRAF3 inhibited the NF-κB activ ation, indicating that TRAF1 or TRAF2 is a positive modulator of LMP1-mediated NF-κB activation, whereas,TRAF3 is a negative modulator. Rather both CTAR1 (carboxy-terminal activating region 1) and CTAR2 domains of LMP1 can independently activate NF-κB by interacting with TRAF proteins. These data indicate that LMP1 interacts TRAF1,2,3 which are important for LMP1-mediated N F-κB activation, and further suggest that signaling from TRAFs may be involved in the progression to malignancy in cells of epithelial origin such as nasophar yngeal carcinoma (NPC).