Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation
HBx is a short-lived protein whose rapid turnover is mainly regulated by ubiquitin-dependent proteasomal degradation pathways. Our prior work identified BAF155 to be one of the HBx binding partners. Since BAF155 has been shown to stabilize other members of the SWI/SNF chromatin remodelling complex b...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1666661 |
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| author | Huijing Chen Yi Zhang Shuangshuang Ye Qiong Wu Youfen Lin Kaiqin Sheng Wannan Chen Xinjian Lin Xu Lin |
| author_facet | Huijing Chen Yi Zhang Shuangshuang Ye Qiong Wu Youfen Lin Kaiqin Sheng Wannan Chen Xinjian Lin Xu Lin |
| author_sort | Huijing Chen |
| collection | DOAJ |
| description | HBx is a short-lived protein whose rapid turnover is mainly regulated by ubiquitin-dependent proteasomal degradation pathways. Our prior work identified BAF155 to be one of the HBx binding partners. Since BAF155 has been shown to stabilize other members of the SWI/SNF chromatin remodelling complex by attenuating their proteasomal degradation, we proposed that BAF155 might also contribute to stabilizing HBx protein in a proteasome-dependent manner. Here we report that BAF155 protected hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation by competing with the 20S proteasome subunit PSMA7 to bind to HBx. BAF155 was found to directly interact with HBx via binding of its SANT domain to the HBx region between amino acid residues 81 and 120. Expression of either full-length BAF155 or SANT domain increased HBx protein levels whereas siRNA-mediated knockdown of endogenous BAF155 reduced HBx protein levels. Increased HBx stability and steady-state level by BAF155 were attributable to inhibition of ubiquitin-independent and PSMA7-mediated protein degradation. Consequently, overexpression of BAF155 enhanced the transcriptional transactivation function of HBx, activated protooncogene expression and inhibited hepatoma cell clonogenicity. These results suggest that BAF155 plays important roles in ubiquitin-independent degradation of HBx, which may be related to the pathogenesis and carcinogenesis of HBV-associated HCC. |
| format | Article |
| id | doaj-art-a445d9dafd2f494a940bb25d13b0e52a |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-a445d9dafd2f494a940bb25d13b0e52a2025-08-20T02:08:14ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-01811393140510.1080/22221751.2019.1666661Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradationHuijing Chen0Yi Zhang1Shuangshuang Ye2Qiong Wu3Youfen Lin4Kaiqin Sheng5Wannan Chen6Xinjian Lin7Xu Lin8Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of ChinaKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of ChinaHBx is a short-lived protein whose rapid turnover is mainly regulated by ubiquitin-dependent proteasomal degradation pathways. Our prior work identified BAF155 to be one of the HBx binding partners. Since BAF155 has been shown to stabilize other members of the SWI/SNF chromatin remodelling complex by attenuating their proteasomal degradation, we proposed that BAF155 might also contribute to stabilizing HBx protein in a proteasome-dependent manner. Here we report that BAF155 protected hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation by competing with the 20S proteasome subunit PSMA7 to bind to HBx. BAF155 was found to directly interact with HBx via binding of its SANT domain to the HBx region between amino acid residues 81 and 120. Expression of either full-length BAF155 or SANT domain increased HBx protein levels whereas siRNA-mediated knockdown of endogenous BAF155 reduced HBx protein levels. Increased HBx stability and steady-state level by BAF155 were attributable to inhibition of ubiquitin-independent and PSMA7-mediated protein degradation. Consequently, overexpression of BAF155 enhanced the transcriptional transactivation function of HBx, activated protooncogene expression and inhibited hepatoma cell clonogenicity. These results suggest that BAF155 plays important roles in ubiquitin-independent degradation of HBx, which may be related to the pathogenesis and carcinogenesis of HBV-associated HCC.https://www.tandfonline.com/doi/10.1080/22221751.2019.1666661Hepatitis B virus X proteinchromatin remodelling factor BAF155ubiquitin-dependent and -independent proteasomal degradationproteasomal subunit PSMA7hpatocellular carcinoma |
| spellingShingle | Huijing Chen Yi Zhang Shuangshuang Ye Qiong Wu Youfen Lin Kaiqin Sheng Wannan Chen Xinjian Lin Xu Lin Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation Emerging Microbes and Infections Hepatitis B virus X protein chromatin remodelling factor BAF155 ubiquitin-dependent and -independent proteasomal degradation proteasomal subunit PSMA7 hpatocellular carcinoma |
| title | Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation |
| title_full | Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation |
| title_fullStr | Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation |
| title_full_unstemmed | Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation |
| title_short | Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation |
| title_sort | chromatin remodelling factor baf155 protects hepatitis b virus x protein hbx from ubiquitin independent proteasomal degradation |
| topic | Hepatitis B virus X protein chromatin remodelling factor BAF155 ubiquitin-dependent and -independent proteasomal degradation proteasomal subunit PSMA7 hpatocellular carcinoma |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1666661 |
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