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

Sha Fu, Juan Wang, Xingwang Hu, Rong Rong Zhou, Yongming Fu, Daolin Tang, Rui Kang, Yan Huang, Lunquan Sun, Ning Li, Xue Gong Fan

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)322-338
Number of pages17
JournalMolecular oncology
Volume12
Issue number3
DOIs
StatePublished - Mar 2018
Externally publishedYes

Keywords

  • acetylation
  • autophagy
  • hepatitis B virus
  • high-mobility group box 1
  • histone deacetylases
  • protein protein interaction

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

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