Regulation mechanism of HCV NS5A on p53 protein transactivity.
- Author:
Guo-zhong GONG
1
;
Yong-fang JIANG
;
Ying-hua ZHU
;
Xian-shi SU
Author Information
- Publication Type:Journal Article
- MeSH: Hepacivirus; genetics; Humans; Promoter Regions, Genetic; Transcriptional Activation; drug effects; Tumor Suppressor Protein p53; drug effects; genetics; metabolism; physiology; Viral Core Proteins; genetics; Viral Nonstructural Proteins; genetics; pharmacology
- From: Chinese Journal of Hepatology 2003;11(3):162-165
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the inhibition effect of HCV NS5A on p53 protein transactivity and its possible mechanism.
METHODSLuciferase reporter gene system was used for the study of p53 transactivity on p21 promoter and electrophorectic mobility-shift assay (EMSA) was applied to observe whether HCV NS5A could suppress the binding ability of p53 protein to its specific DNA sequence.
RESULTSEndogenous p53 protein could stimulate p21 promoter activity, and the relative luciferase activity increased significantly (3.49 x 10(5) vs 0.60 x 10(5), t = 5.92, P<0.01). Exogenous p53 protein also up-regulated p21 promoter driving luciferase expression, comparing to the control group (0.47 x 10(5)), the relative luciferase activity increased (5.63 x 10(5)) obviously (t = 10.12, P<0.01). HCV NS5A protein inhibited both endogenous and exogenous p53 transactivity on p21 promoter in a dose-dependent manner (F > or = 20.71, P<0.01). In the experiment of EMSA, p53 could bind to its specific DNA sequence, but when co-transfected with HCV NS5A expressing vector, the p53 binding affinity to its DNA decreased.
CONCLUSIONHCV NS5A can inhibit p53 protein transactivity on p21 promoter through its inhibiting of p53 binding ability to the specific DNA sequence.
