Crosstalk between hepatitis B virus X and high‐mobility group box 1 facilitates autophagy in hepatocytes
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 i...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-03-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12165 |
| _version_ | 1818885568176586752 |
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| author | Sha Fu Juan Wang Xingwang Hu Rong‐rong Zhou Yongming Fu Daolin Tang Rui Kang Yan Huang Lunquan Sun Ning Li Xue‐Gong Fan |
| author_facet | Sha Fu Juan Wang Xingwang Hu Rong‐rong Zhou Yongming Fu Daolin Tang Rui Kang Yan Huang Lunquan Sun Ning Li Xue‐Gong Fan |
| author_sort | Sha Fu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T16:07:30Z |
| format | Article |
| id | doaj.art-b3c88aac8d474df284e0592b822094ec |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-19T16:07:30Z |
| publishDate | 2018-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-b3c88aac8d474df284e0592b822094ec2022-12-21T20:14:48ZengWileyMolecular Oncology1574-78911878-02612018-03-0112332233810.1002/1878-0261.12165Crosstalk between hepatitis B virus X and high‐mobility group box 1 facilitates autophagy in hepatocytesSha Fu0Juan Wang1Xingwang Hu2Rong‐rong Zhou3Yongming Fu4Daolin Tang5Rui Kang6Yan Huang7Lunquan Sun8Ning Li9Xue‐Gong Fan10Department of Infectious Diseases Hunan Key Laboratory of Viral Hepatitis Xiangya Hospital Central South University Changsha ChinaDepartment of Infectious Diseases Hunan Key Laboratory of Viral Hepatitis Xiangya Hospital Central South University Changsha ChinaDepartment of Infectious Diseases Hunan Key Laboratory of Viral Hepatitis Xiangya Hospital Central South University Changsha ChinaDepartment of Infectious Diseases Hunan Key Laboratory of Viral Hepatitis Xiangya Hospital Central South University Changsha ChinaDepartment of Infectious Diseases Hunan Key Laboratory of Viral Hepatitis Xiangya Hospital Central South University Changsha ChinaDepartment of Surgery University of Pittsburgh PA USADepartment of Surgery University of Pittsburgh PA USADepartment of Infectious Diseases Hunan Key Laboratory of Viral Hepatitis Xiangya Hospital Central South University Changsha ChinaCenter for Molecular Medicine Xiangya Hospital Central South University Changsha ChinaDepartment of Blood Transfusion Xiangya Hospital Central South University Changsha ChinaDepartment of Infectious Diseases Hunan Key Laboratory of Viral Hepatitis Xiangya Hospital Central South University Changsha ChinaHepatitis 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.https://doi.org/10.1002/1878-0261.12165acetylationautophagyhepatitis B virushigh‐mobility group box 1histone deacetylasesprotein protein interaction |
| spellingShingle | Sha Fu Juan Wang Xingwang Hu Rong‐rong Zhou Yongming Fu Daolin Tang Rui Kang Yan Huang Lunquan Sun Ning Li Xue‐Gong Fan Crosstalk between hepatitis B virus X and high‐mobility group box 1 facilitates autophagy in hepatocytes Molecular Oncology acetylation autophagy hepatitis B virus high‐mobility group box 1 histone deacetylases protein protein interaction |
| title | Crosstalk between hepatitis B virus X and high‐mobility group box 1 facilitates autophagy in hepatocytes |
| title_full | Crosstalk between hepatitis B virus X and high‐mobility group box 1 facilitates autophagy in hepatocytes |
| title_fullStr | Crosstalk between hepatitis B virus X and high‐mobility group box 1 facilitates autophagy in hepatocytes |
| title_full_unstemmed | Crosstalk between hepatitis B virus X and high‐mobility group box 1 facilitates autophagy in hepatocytes |
| title_short | Crosstalk between hepatitis B virus X and high‐mobility group box 1 facilitates autophagy in hepatocytes |
| title_sort | crosstalk between hepatitis b virus x and high mobility group box 1 facilitates autophagy in hepatocytes |
| topic | acetylation autophagy hepatitis B virus high‐mobility group box 1 histone deacetylases protein protein interaction |
| url | https://doi.org/10.1002/1878-0261.12165 |
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