GCN5 acetyltransferase inhibits PGC1α-induced hepatitis B virus biosynthesis
Hepatitis B virus (HBV) biosynthesis is primarily restricted to hepatocytes due to the governing of liver-enriched nuclear receptors (NRs) on viral RNA synthesis. The liver-enriched NR hepatocyte nuclear factor 4α (HNF4α), the key regulator of genes implicated in hepatic glucose metabolism, is also...
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| Veröffentlicht in: | Virologica Sinica 2013-08, Vol.28 (4), p.216-222 |
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| creator | Tian, Xiaohui Zhao, Fei Cheng, Zhikui Zhou, Ming Zhi, Xiaoguang Li, Jiafu Hu, Kanghong |
| description | Hepatitis B virus (HBV) biosynthesis is primarily restricted to hepatocytes due to the governing of liver-enriched nuclear receptors (NRs) on viral RNA synthesis. The liver-enriched NR hepatocyte nuclear factor 4α (HNF4α), the key regulator of genes implicated in hepatic glucose metabolism, is also a primary determinant of HBV pregenomic RNA synthesis and HBV replication. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) coactivates and further enhances the effect of HNF4α on HBV biosynthesis. Here, we showed that the acetyltransferase General Control Non-repressed Protein 5 (GCN5) acetylated PGC1α, leading to alteration of PGC1α from a transcriptionally active state into an inactive state. As a result, the coactivation activity of PGC1α on HBV transcription and replication was suppressed. Apparently, an acetylation site mutant of PGC1α (PGC1αR13) still had coactivation activity as GCN5 could not suppress the coactivation activity of the mutant. Moreover, a catalytically inactive acetyltransferase mutant GCN5m, due to the loss of acetylation activity, failed to inhibit the coactivation function of PGC1α in HBV biosynthesis. Our results demonstrate that GCN5, through its acetyltransferase activity, inhibits PGC1α-induced enhancement of HBV transcription and replication both in vitro and in vivo. |
| doi_str_mv | 10.1007/s12250-013-3344-3 |
| format | Article |
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The liver-enriched NR hepatocyte nuclear factor 4α (HNF4α), the key regulator of genes implicated in hepatic glucose metabolism, is also a primary determinant of HBV pregenomic RNA synthesis and HBV replication. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) coactivates and further enhances the effect of HNF4α on HBV biosynthesis. Here, we showed that the acetyltransferase General Control Non-repressed Protein 5 (GCN5) acetylated PGC1α, leading to alteration of PGC1α from a transcriptionally active state into an inactive state. As a result, the coactivation activity of PGC1α on HBV transcription and replication was suppressed. Apparently, an acetylation site mutant of PGC1α (PGC1αR13) still had coactivation activity as GCN5 could not suppress the coactivation activity of the mutant. Moreover, a catalytically inactive acetyltransferase mutant GCN5m, due to the loss of acetylation activity, failed to inhibit the coactivation function of PGC1α in HBV biosynthesis. Our results demonstrate that GCN5, through its acetyltransferase activity, inhibits PGC1α-induced enhancement of HBV transcription and replication both in vitro and in vivo.</description><identifier>ISSN: 1674-0769</identifier><identifier>EISSN: 1995-820X</identifier><identifier>DOI: 10.1007/s12250-013-3344-3</identifier><identifier>PMID: 23913178</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Acetylation ; Animals ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; biosynthesis ; Female ; glucose ; Hepatitis B virus ; Hepatitis B virus - physiology ; hepatocytes ; Hepatocytes - virology ; Humans ; Medical Microbiology ; Mice ; Mice, Inbred BALB C ; Microbial Genetics and Genomics ; Microbiology ; mutants ; Oncology ; p300-CBP Transcription Factors - metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Protein Processing, Post-Translational ; receptors ; regulator genes ; Research Article ; RNA ; Transcription Factors - metabolism ; Transcription, Genetic ; Virology ; Virus Replication</subject><ispartof>Virologica Sinica, 2013-08, Vol.28 (4), p.216-222</ispartof><rights>Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2013</rights><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4454-7a0fae9ddf99ae4fffc5113098beb6a7b640f77aacd95ee790a48975f54cd0a63</citedby><cites>FETCH-LOGICAL-c4454-7a0fae9ddf99ae4fffc5113098beb6a7b640f77aacd95ee790a48975f54cd0a63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.wanfangdata.com.cn/images/PeriodicalImages/zgbdx/zgbdx.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208399/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208399/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27928,27929,41492,42561,51323,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23913178$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tian, Xiaohui</creatorcontrib><creatorcontrib>Zhao, Fei</creatorcontrib><creatorcontrib>Cheng, Zhikui</creatorcontrib><creatorcontrib>Zhou, Ming</creatorcontrib><creatorcontrib>Zhi, Xiaoguang</creatorcontrib><creatorcontrib>Li, Jiafu</creatorcontrib><creatorcontrib>Hu, Kanghong</creatorcontrib><title>GCN5 acetyltransferase inhibits PGC1α-induced hepatitis B virus biosynthesis</title><title>Virologica Sinica</title><addtitle>Virol. Sin</addtitle><addtitle>Virol Sin</addtitle><description>Hepatitis B virus (HBV) biosynthesis is primarily restricted to hepatocytes due to the governing of liver-enriched nuclear receptors (NRs) on viral RNA synthesis. The liver-enriched NR hepatocyte nuclear factor 4α (HNF4α), the key regulator of genes implicated in hepatic glucose metabolism, is also a primary determinant of HBV pregenomic RNA synthesis and HBV replication. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) coactivates and further enhances the effect of HNF4α on HBV biosynthesis. Here, we showed that the acetyltransferase General Control Non-repressed Protein 5 (GCN5) acetylated PGC1α, leading to alteration of PGC1α from a transcriptionally active state into an inactive state. As a result, the coactivation activity of PGC1α on HBV transcription and replication was suppressed. Apparently, an acetylation site mutant of PGC1α (PGC1αR13) still had coactivation activity as GCN5 could not suppress the coactivation activity of the mutant. Moreover, a catalytically inactive acetyltransferase mutant GCN5m, due to the loss of acetylation activity, failed to inhibit the coactivation function of PGC1α in HBV biosynthesis. Our results demonstrate that GCN5, through its acetyltransferase activity, inhibits PGC1α-induced enhancement of HBV transcription and replication both in vitro and in vivo.</description><subject>Acetylation</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>biosynthesis</subject><subject>Female</subject><subject>glucose</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - physiology</subject><subject>hepatocytes</subject><subject>Hepatocytes - virology</subject><subject>Humans</subject><subject>Medical Microbiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbial Genetics and Genomics</subject><subject>Microbiology</subject><subject>mutants</subject><subject>Oncology</subject><subject>p300-CBP Transcription Factors - metabolism</subject><subject>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</subject><subject>Protein Processing, Post-Translational</subject><subject>receptors</subject><subject>regulator genes</subject><subject>Research Article</subject><subject>RNA</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Virology</subject><subject>Virus Replication</subject><issn>1674-0769</issn><issn>1995-820X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAUhSMEoqXwAGwgK8QmcB3bcbxBghEMSOVHgkrsrJvkOuMq40ztpDC8FS_CM-FRSoENYmVL_u7xOfdk2X0GTxiAehpZWUoogPGCcyEKfiM7ZlrLoi7h8810r5QoQFX6KLsT4zlAVdac386OSq4ZZ6o-zt6uV-9kji1N-2EK6KOlgJFy5zeucVPMP6xX7Mf3wvlubqnLN7TDyU0u5i_ySxfmmDdujHs_bSi6eDe7ZXGIdO_qPMnOXr38tHpdnL5fv1k9Py1aIaQoFIJF0l1ntUYS1tpWMsZB1w01FaqmEmCVQmw7LYmUBhS1VtJK0XaAFT_Jni26u7nZUteST94Hswtui2FvRnTm7xfvNqYfL01aTM21TgKPFoEv6C363pyPc_DJsvnWN93XMq0UBIBI4OOrn8J4MVOczNbFloYBPY1zNEwIzlWlGP8PlNVMaCZkQtmCtmGMMZC9ts7AHKo1S7Um-TCHas1B_sGfma8nfnWZgHIBYnryPYXfof6l-nAZsjga7IOL5uxjip_CQ1VxqflP9bW5Tw</recordid><startdate>201308</startdate><enddate>201308</enddate><creator>Tian, Xiaohui</creator><creator>Zhao, Fei</creator><creator>Cheng, Zhikui</creator><creator>Zhou, Ming</creator><creator>Zhi, Xiaoguang</creator><creator>Li, Jiafu</creator><creator>Hu, Kanghong</creator><general>Springer-Verlag</general><general>Springer Berlin Heidelberg</general><general>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China%Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan 430030, China%State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China</general><general>Biomedical Center, Hubei University of Technology, Wuhan 430068, China</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7U9</scope><scope>H94</scope><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope><scope>5PM</scope></search><sort><creationdate>201308</creationdate><title>GCN5 acetyltransferase inhibits PGC1α-induced hepatitis B virus biosynthesis</title><author>Tian, Xiaohui ; Zhao, Fei ; Cheng, Zhikui ; Zhou, Ming ; Zhi, Xiaoguang ; Li, Jiafu ; Hu, Kanghong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4454-7a0fae9ddf99ae4fffc5113098beb6a7b640f77aacd95ee790a48975f54cd0a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetylation</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>biosynthesis</topic><topic>Female</topic><topic>glucose</topic><topic>Hepatitis B virus</topic><topic>Hepatitis B virus - physiology</topic><topic>hepatocytes</topic><topic>Hepatocytes - virology</topic><topic>Humans</topic><topic>Medical Microbiology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbial Genetics and Genomics</topic><topic>Microbiology</topic><topic>mutants</topic><topic>Oncology</topic><topic>p300-CBP Transcription Factors - metabolism</topic><topic>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</topic><topic>Protein Processing, Post-Translational</topic><topic>receptors</topic><topic>regulator genes</topic><topic>Research Article</topic><topic>RNA</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Virology</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tian, Xiaohui</creatorcontrib><creatorcontrib>Zhao, Fei</creatorcontrib><creatorcontrib>Cheng, Zhikui</creatorcontrib><creatorcontrib>Zhou, Ming</creatorcontrib><creatorcontrib>Zhi, Xiaoguang</creatorcontrib><creatorcontrib>Li, Jiafu</creatorcontrib><creatorcontrib>Hu, Kanghong</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Virologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tian, Xiaohui</au><au>Zhao, Fei</au><au>Cheng, Zhikui</au><au>Zhou, Ming</au><au>Zhi, Xiaoguang</au><au>Li, Jiafu</au><au>Hu, Kanghong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GCN5 acetyltransferase inhibits PGC1α-induced hepatitis B virus biosynthesis</atitle><jtitle>Virologica Sinica</jtitle><stitle>Virol. Sin</stitle><addtitle>Virol Sin</addtitle><date>2013-08</date><risdate>2013</risdate><volume>28</volume><issue>4</issue><spage>216</spage><epage>222</epage><pages>216-222</pages><issn>1674-0769</issn><eissn>1995-820X</eissn><abstract>Hepatitis B virus (HBV) biosynthesis is primarily restricted to hepatocytes due to the governing of liver-enriched nuclear receptors (NRs) on viral RNA synthesis. The liver-enriched NR hepatocyte nuclear factor 4α (HNF4α), the key regulator of genes implicated in hepatic glucose metabolism, is also a primary determinant of HBV pregenomic RNA synthesis and HBV replication. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) coactivates and further enhances the effect of HNF4α on HBV biosynthesis. Here, we showed that the acetyltransferase General Control Non-repressed Protein 5 (GCN5) acetylated PGC1α, leading to alteration of PGC1α from a transcriptionally active state into an inactive state. As a result, the coactivation activity of PGC1α on HBV transcription and replication was suppressed. Apparently, an acetylation site mutant of PGC1α (PGC1αR13) still had coactivation activity as GCN5 could not suppress the coactivation activity of the mutant. Moreover, a catalytically inactive acetyltransferase mutant GCN5m, due to the loss of acetylation activity, failed to inhibit the coactivation function of PGC1α in HBV biosynthesis. Our results demonstrate that GCN5, through its acetyltransferase activity, inhibits PGC1α-induced enhancement of HBV transcription and replication both in vitro and in vivo.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>23913178</pmid><doi>10.1007/s12250-013-3344-3</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Virologica Sinica, 2013-08, Vol.28 (4), p.216-222 |
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| source | MEDLINE; SpringerNature Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Acetylation Animals Biochemistry Biomedical and Life Sciences Biomedicine biosynthesis Female glucose Hepatitis B virus Hepatitis B virus - physiology hepatocytes Hepatocytes - virology Humans Medical Microbiology Mice Mice, Inbred BALB C Microbial Genetics and Genomics Microbiology mutants Oncology p300-CBP Transcription Factors - metabolism Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Protein Processing, Post-Translational receptors regulator genes Research Article RNA Transcription Factors - metabolism Transcription, Genetic Virology Virus Replication |
| title | GCN5 acetyltransferase inhibits PGC1α-induced hepatitis B virus biosynthesis |
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