Protein phosphatase 4 catalytic subunit (PP4C) increases hepatitis B virus X protein levels and promotes its biological functions
10.3760/cma.j.cn112309-20230615-00173
- VernacularTitle:蛋白质磷酸酶4催化亚基调控乙型肝炎病毒X蛋白水平及生物学功能
- Author:
Qiuran WANG
1
;
Yili ZHENG
;
Tianmin WU
;
Yuanyuan CHEN
;
Wenjun LIAO
;
Lu ZHANG
;
Xu LIN
;
Qiong WU
;
Wannan CHEN
Author Information
1. 福建医科大学基础医学院，消化道恶性肿瘤教育部重点实验室，福州 350122
- Keywords:
HBx;
Protein phosphatase 4 catalytic subunit;
Dephosphorylation;
Hepatocellular carcinoma;
Migration;
Invasion
- From:
Chinese Journal of Microbiology and Immunology
2023;43(7):509-516
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of protein phosphatase 4 catalytic subunit (PP4C) in regulating hepatitis B virus X protein (HBx) levels and its effects on the biological functions of HBx, thus to provide a potential therapeutic targets for hepatitis B virus (HBV)-related hepatocellular carcinoma.Methods:In vivo and in vitro interactions between HBx and PP4C were analyzed by co-immunoprecipitation (Co-IP) and GST pull-down assay. Recombinant plasmids of PP4C and HBx were co-transfected with Lipofectamine 3000 reagents into hepatoma cells to detect the protein levels of HBx by Western blot. The half-life of HBx in the transfected cells treated with cycloheximide (CHX) were detected. The phosphorylation assay was used to evaluate the effects of PP4C on HBx phosphorylation. CCK8 assay, wound healing assay and Matrigel invasion chamber assay were used to analyze the effects of PP4C on the biological functions of HBx. Results:PP4C interacted with HBx in vivo and in vitro. PP4C overexpression significantly increased the protein level and stability of HBx and the phosphorylation assay confirmed that PP4C overexpression decreased the serine phosphorylation of HBx in hepatoma cells. PP4C overexpression enhanced the migration and invasion of hepatoma cells, but had no significant effects on the proliferation. Conclusions:The interactions between HBx and PP4C promoted the stability of HBx and ultimately enhanced the migration and invasion of hepatoma cells, and the mechanisms might be related to the decrease of HBx serine phosphorylation by PP4C. This study provided a theoretical basis for further investigation of the pathogenic mechanisms of HBx, and targeting PP4C and HBx interaction might provide insights for developing novel treatment for HBV-related hepatocellular carcinoma.
