The N-Glycosylation Modification of LHBs (Large Surface Proteins of HBV) Effects on Endoplasmic Reticulum Stress, Cell Proliferation and its Secretion

authors:

avatar Wenxiang Liu 1 , avatar Yongmei Cao 2 , avatar Tao Wang 1 , avatar Guoan Xiang 3 , avatar Jiangyang Lu 4 , * , avatar Jinqian Zhang 5 , ** , avatar Peng Hou 1 , ***

Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China
International Mongolian Hospital, Hohhot of Inner Mongolia, Hohhot, China
Department of General Surgery, the Second People's Hospital of Guangdong Province, Guangzhou, China
Department of Pathology, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
Corresponding Authors:
Hepatitis Monthly: Vol.13, issue 9; 12280
published online: September 7, 2013
article type: Research Article
received: May 17, 2013
accepted: August 24, 2013
DOI: https://doi.org/10.5812/hepatmon.12280

how to cite: Liu W, Cao Y, Wang T, Xiang G, Lu J, et al. The N-Glycosylation Modification of LHBs (Large Surface Proteins of HBV) Effects on Endoplasmic Reticulum Stress, Cell Proliferation and its Secretion. Hepat Mon. 2013;13(9):12280. https://doi.org/10.5812/hepatmon.12280.

Abstract

Background:

The mutations of LHBs in pre-S, especially in pre-S2, are definitive in hepatocellular carcinoma (HCC) associated with HBV. However, the mechanisms of the N-glycosylation modification in LHBs are unclear. The N-glycosylation modification of LHBs affects Endoplasmic Reticulum stress, cell proliferation and its secretion which was further studied.

Objectives:

The objectives of our studies was to indentified that modification of LHBs by N glycosylation modulate their secretion, affect ER stress or expression of cycling, cell cycle and proliferation.

Materials and Methods:

The LHBs was mutated; then expression of proteins related to endoplasmic reticulum stress and EAED path of L02 cells affected by LHBs and its mutations was evaluated. LHBs proteins bound to multiubiquitin chains and its glycosylation motif were studied. The subcellular localization and secretion of LHBs and its mutations were identified. The effect on cell cycle and proliferation by LHBs and its mutations were detected.

Results:

These data demonstrated that the N-glycosylation motifs of LHBs were associated with ER stress. The N15S, N123S, and N177S mutated LHBs proteins could induce overexpression of EDEM in L02 cells. LHBs and its mutated proteins contained p62-derived UBA domain, which could affect expression of cyclins. The subcellular localization of LHBs in endoplasmic reticulum was similar to its mutations. The secretion of LHBs was blocked by N320K mutation, which could induce an increase in G1 phase and inhibition of S phase, and inhibited mitotic entry.

Conclusions:

In conclusion, our studies powerfully demonstrated that modification of LHBs by N glycosylation could modulate their secretion, affect ER stress or expression of cycling, cell cycle and proliferation. The N320K may be the key sites N-linked glycosylation modification of LHBs. It may be a mechanism of HBV-induced HCC.

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