Hepatitis C Virus NS5A Protein Modulates Transcription through a Novel Cellular Transcription Factor SRCAP
Hepatitis C virus NS5A protein transcriptionally modulates cellular genes and promotes cell growth. NS5A is likely to exert its activity in concert with cellular factor(s). Using a yeast two-hybrid screen, we have demonstrated that NS5A interacts with the C-terminal end of a newly identified cellula...
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| Veröffentlicht in: | The Journal of biological chemistry 2000-03, Vol.275 (10), p.7184-7188 |
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| container_end_page | 7188 |
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| container_issue | 10 |
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| container_title | The Journal of biological chemistry |
| container_volume | 275 |
| creator | Ghosh, Asish K. Majumder, Mainak Steele, Robert Yaciuk, Peter Chrivia, John Ray, Ranjit Ray, Ratna B. |
| description | Hepatitis C virus NS5A protein transcriptionally modulates cellular genes and promotes cell growth. NS5A is likely to exert its activity in concert with cellular factor(s). Using a yeast two-hybrid screen, we have demonstrated that NS5A interacts with the C-terminal end of a newly identified cellular transcription factor, SRCAP. The authenticity of this interaction was verified by a mammalian two-hybrid assay, in vitro pull-down experiment, and anin vivo coimmunoprecipitation assay in human hepatoma (HepG2) cells. An in vitro transient transfection assay demonstrated that SRCAP can efficiently activate transcription when recruited by the Gal4 DNA-binding domain to the promoter. However, down-regulation of p21 promoter activity by NS5A was enhanced following ectopic expression of SRCAP. Together these results suggest that the interaction of NS5A and SRCAP may be one of the mechanisms by which NS5A exerts its effect on cell growth regulation contributing to hepatitis C virus-mediated pathogenesis. |
| doi_str_mv | 10.1074/jbc.275.10.7184 |
| format | Article |
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NS5A is likely to exert its activity in concert with cellular factor(s). Using a yeast two-hybrid screen, we have demonstrated that NS5A interacts with the C-terminal end of a newly identified cellular transcription factor, SRCAP. The authenticity of this interaction was verified by a mammalian two-hybrid assay, in vitro pull-down experiment, and anin vivo coimmunoprecipitation assay in human hepatoma (HepG2) cells. An in vitro transient transfection assay demonstrated that SRCAP can efficiently activate transcription when recruited by the Gal4 DNA-binding domain to the promoter. However, down-regulation of p21 promoter activity by NS5A was enhanced following ectopic expression of SRCAP. Together these results suggest that the interaction of NS5A and SRCAP may be one of the mechanisms by which NS5A exerts its effect on cell growth regulation contributing to hepatitis C virus-mediated pathogenesis.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.275.10.7184</identifier><identifier>PMID: 10702287</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adenosine Triphosphatases - metabolism ; Fluorescent Antibody Technique ; Gal4 protein ; Hepacivirus - pathogenicity ; Hepatitis C virus ; Humans ; NS5A protein ; p21 protein ; Precipitin Tests ; Promoter Regions, Genetic ; Protein-Serine-Threonine Kinases - metabolism ; SRCAP protein ; Transcription Factors - metabolism ; Transcription, Genetic ; Tumor Cells, Cultured</subject><ispartof>The Journal of biological chemistry, 2000-03, Vol.275 (10), p.7184-7188</ispartof><rights>2000 © 2000 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-6cc731db94a3e8de8a2d15b060f8ef6c469d19f379defbdf9cbe5059e06702e23</citedby><cites>FETCH-LOGICAL-c443t-6cc731db94a3e8de8a2d15b060f8ef6c469d19f379defbdf9cbe5059e06702e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27925,27926</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10702287$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ghosh, Asish K.</creatorcontrib><creatorcontrib>Majumder, Mainak</creatorcontrib><creatorcontrib>Steele, Robert</creatorcontrib><creatorcontrib>Yaciuk, Peter</creatorcontrib><creatorcontrib>Chrivia, John</creatorcontrib><creatorcontrib>Ray, Ranjit</creatorcontrib><creatorcontrib>Ray, Ratna B.</creatorcontrib><title>Hepatitis C Virus NS5A Protein Modulates Transcription through a Novel Cellular Transcription Factor SRCAP</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Hepatitis C virus NS5A protein transcriptionally modulates cellular genes and promotes cell growth. NS5A is likely to exert its activity in concert with cellular factor(s). Using a yeast two-hybrid screen, we have demonstrated that NS5A interacts with the C-terminal end of a newly identified cellular transcription factor, SRCAP. The authenticity of this interaction was verified by a mammalian two-hybrid assay, in vitro pull-down experiment, and anin vivo coimmunoprecipitation assay in human hepatoma (HepG2) cells. An in vitro transient transfection assay demonstrated that SRCAP can efficiently activate transcription when recruited by the Gal4 DNA-binding domain to the promoter. However, down-regulation of p21 promoter activity by NS5A was enhanced following ectopic expression of SRCAP. Together these results suggest that the interaction of NS5A and SRCAP may be one of the mechanisms by which NS5A exerts its effect on cell growth regulation contributing to hepatitis C virus-mediated pathogenesis.</description><subject>Adenosine Triphosphatases - metabolism</subject><subject>Fluorescent Antibody Technique</subject><subject>Gal4 protein</subject><subject>Hepacivirus - pathogenicity</subject><subject>Hepatitis C virus</subject><subject>Humans</subject><subject>NS5A protein</subject><subject>p21 protein</subject><subject>Precipitin Tests</subject><subject>Promoter Regions, Genetic</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>SRCAP protein</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Tumor Cells, Cultured</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFr3DAQhUVpaLZpz70VQaE3byRLsq3jYpqmkCahSUtvQpbGsRavtZHklP77anEOJRAyl2Hge4-ZeQh9oGRNSc1Pt51Zl7XIw7qmDX-FVpQ0rGCC_n6NVoSUtJClaI7R2xi3JBeX9A06zlpSlk29Qttz2Ovkkou4xb9cmCO-vBEbfB18Ajfh797Oo04Q8W3QUzTB7ZPzE05D8PPdgDW-9A8w4hbGMYPhCXamTfIB3_xoN9fv0FGvxwjvH_sJ-nn25bY9Ly6uvn5rNxeF4ZylojKmZtR2kmsGjYVGl5aKjlSkb6CvDK-kpbJntbTQd7aXpgNBhARS5aOgZCfo8-K7D_5-hpjUzkWT99MT-DmqmkguGsFeBGktCCP84Hi6gCb4GAP0ah_cToe_ihJ1yEHlHFTO4TAfcsiKj4_Wc7cD-x-_PD4DnxZgcHfDHxdAdc6bAXZPbORCQf7Xg4OgonEwGbBZYZKy3j27wj_pX6M0</recordid><startdate>20000310</startdate><enddate>20000310</enddate><creator>Ghosh, Asish K.</creator><creator>Majumder, Mainak</creator><creator>Steele, Robert</creator><creator>Yaciuk, Peter</creator><creator>Chrivia, John</creator><creator>Ray, Ranjit</creator><creator>Ray, Ratna B.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20000310</creationdate><title>Hepatitis C Virus NS5A Protein Modulates Transcription through a Novel Cellular Transcription Factor SRCAP</title><author>Ghosh, Asish K. ; Majumder, Mainak ; Steele, Robert ; Yaciuk, Peter ; Chrivia, John ; Ray, Ranjit ; Ray, Ratna B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-6cc731db94a3e8de8a2d15b060f8ef6c469d19f379defbdf9cbe5059e06702e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adenosine Triphosphatases - metabolism</topic><topic>Fluorescent Antibody Technique</topic><topic>Gal4 protein</topic><topic>Hepacivirus - pathogenicity</topic><topic>Hepatitis C virus</topic><topic>Humans</topic><topic>NS5A protein</topic><topic>p21 protein</topic><topic>Precipitin Tests</topic><topic>Promoter Regions, Genetic</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>SRCAP protein</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ghosh, Asish K.</creatorcontrib><creatorcontrib>Majumder, Mainak</creatorcontrib><creatorcontrib>Steele, Robert</creatorcontrib><creatorcontrib>Yaciuk, Peter</creatorcontrib><creatorcontrib>Chrivia, John</creatorcontrib><creatorcontrib>Ray, Ranjit</creatorcontrib><creatorcontrib>Ray, Ratna B.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ghosh, Asish K.</au><au>Majumder, Mainak</au><au>Steele, Robert</au><au>Yaciuk, Peter</au><au>Chrivia, John</au><au>Ray, Ranjit</au><au>Ray, Ratna B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatitis C Virus NS5A Protein Modulates Transcription through a Novel Cellular Transcription Factor SRCAP</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2000-03-10</date><risdate>2000</risdate><volume>275</volume><issue>10</issue><spage>7184</spage><epage>7188</epage><pages>7184-7188</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Hepatitis C virus NS5A protein transcriptionally modulates cellular genes and promotes cell growth. NS5A is likely to exert its activity in concert with cellular factor(s). Using a yeast two-hybrid screen, we have demonstrated that NS5A interacts with the C-terminal end of a newly identified cellular transcription factor, SRCAP. The authenticity of this interaction was verified by a mammalian two-hybrid assay, in vitro pull-down experiment, and anin vivo coimmunoprecipitation assay in human hepatoma (HepG2) cells. An in vitro transient transfection assay demonstrated that SRCAP can efficiently activate transcription when recruited by the Gal4 DNA-binding domain to the promoter. However, down-regulation of p21 promoter activity by NS5A was enhanced following ectopic expression of SRCAP. 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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenosine Triphosphatases - metabolism Fluorescent Antibody Technique Gal4 protein Hepacivirus - pathogenicity Hepatitis C virus Humans NS5A protein p21 protein Precipitin Tests Promoter Regions, Genetic Protein-Serine-Threonine Kinases - metabolism SRCAP protein Transcription Factors - metabolism Transcription, Genetic Tumor Cells, Cultured |
| title | Hepatitis C Virus NS5A Protein Modulates Transcription through a Novel Cellular Transcription Factor SRCAP |
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