Crosstalk between hepatitis B virus X and high‐mobility group box 1 facilitates autophagy in hepatocytes

Molecular Oncology

Lunquan Sun¹  Ning Li²  Yan Huang³  Juan Wang³  Xue‐Gong Fan³  Yongming Fu³  Xingwang Hu³  Sha Fu³  Rong‐rong Zhou³  Rui Kang⁴  Daolin Tang⁴ 

[1] Center for Molecular Medicine Xiangya Hospital Central South University Changsha China;Department of Blood Transfusion Xiangya Hospital Central South University Changsha China;Department of Infectious Diseases Hunan Key Laboratory of Viral Hepatitis Xiangya Hospital Central South University Changsha China;Department of Surgery University of Pittsburgh PA USA;

关键词: acetylation;    autophagy;    hepatitis B virus;    high‐mobility group box 1;    histone deacetylases;    protein protein interaction;   

DOI  :  10.1002/1878-0261.12165

来源: DOAJ

【 摘 要 】

Hepatitis B virus (HBV) X (HBx) protein is a pivotal regulator of HBV‐triggered autophagy. However, the role of HBx‐induced epigenetic changes in autophagy remains largely unknown. The cytoplasmic (Cyt) high‐mobility group box 1 (HMGB1) has been identified as a positive regulator of autophagy, and its Cyt translocation is closely associated with its acetylation status. Here, we evaluated the function of HMGB1 in HBx‐mediated autophagy and its association with histone deacetylase (HDAC). Using cell lines with enforced expression of HBx, we demonstrated that HBx upregulated the expression of HMGB1 and promoted its Cyt translocation by acetylation to facilitate autophagy. We further identified the underlying mechanism by which decreased nuclear HDAC activity and expression levels contribute to the HBx‐promoted hyperacetylation and subsequent translocation of HMGB1. We also identified the HDAC1 isoform as a critical factor in regulating this phenomenon. In addition, HBx bound to HMGB1 in the cytoplasm, which triggered autophagy in hepatocytes. Pharmacological inhibition of HMGB1 Cyt translocation with ethyl pyruvate prevented HBx‐induced autophagy. These results demonstrate a novel function of acetylated HMGB1 in HBx‐mediated autophagy in hepatocytes.

【 授权许可】

Unknown