Hepatitis B virus X protein inhibits apoptosis by modulating endoplasmic reticulum stress response
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 1609 views | HTML 2379 views | ?
Jia Li1,4, Jiang He2,3, Yongming Fu1, Xingwang Hu1, Lun-Quan Sun2,3, Yan Huang1 and Xuegong Fan1
1Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, China
2Center for Molecular Medicine, Center for Molecular Medicine, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha 410078, China
3Key Laboratory of Molecular Radiation Oncology, Changsha 410008, China
4Department of Emergency, Xiangya Hospital, Central South University, Changsha 410008, China
Xuegong Fan, email: [email protected]
Yan Huang, email: [email protected]
Keywords: HBV; HBx; hepatocellular carcinoma; ER stress; apoptosis
Received: March 15, 2017 Accepted: August 26, 2017 Published: October 06, 2017
Chronic Hepatitis B virus (HBV) infection is a major risk of hepatocellular carcinoma (HCC) worldwide. Hepatitis B virus X protein (HBx) is encoded by one of the four open reading frames of HBV, and is well known as an important coactivator for HBV replication and HBV-associated hepatocellular carcinogenesis. However, its role in keeping cells from apoptosis to promote HCC proliferation remains controversial. Here, we used HBx expressing HCC cells as a model, to investigate the mechanism of HBx-mediated cellular response to endoplasmic reticulum (ER) stress. We found that HBx protein was localized in ER lumen and interacted with GRP78 directly. This interaction resulted in suppression of eIF2α phosphorylation, inhibited expression of ATF4/CHOP/Bcl-2, and reduced cleavage of poly ADP-ribose polymerase (PARP) and level of γH2AX, thus preventing HCC cells from cell death and negatively regulating DNA repair. This study reveals a novel mechanism of the HBx-mediated oncogenesis and provides a basis for potential HBx-targeted therapeutic intervention of HCC.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.