HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs
The E7 proteins of human papillomaviruses (HPVs) contribute to oncogenesis by associating with Rb family members as well class I histone deacetylases (HDACs). The binding of HDACs is also important for the maintenance of viral episomes during the differentiation‐dependent productive life cycle. The...
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description | The E7 proteins of human papillomaviruses (HPVs) contribute to oncogenesis by associating with Rb family members as well class I histone deacetylases (HDACs). The binding of HDACs is also important for the maintenance of viral episomes during the differentiation‐dependent productive life cycle. The effects of E7 and other viral proteins on E2F family members were examined in differentiating keratinocytes. E7 was found to specifically activate E2F2 transcription in suprabasal keratinocytes through its ability to bind HDACs. Chromatin immunoprecipitation assays demonstrated that, in differentiating cells, E7 acts to inhibit HDAC binding to the E2F2 promoter resulting in activation of expression. Reduction of E2F2 levels through the use of siRNA confirmed that E2F2 expression facilitated HPV replication but its loss did not affect cell proliferation. Our study demonstrates a mechanism by which binding of HDACs to E7 directly modulates viral replication and identifies E2F2 as a possible target for antiviral therapies. |
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The binding of HDACs is also important for the maintenance of viral episomes during the differentiation‐dependent productive life cycle. The effects of E7 and other viral proteins on E2F family members were examined in differentiating keratinocytes. E7 was found to specifically activate E2F2 transcription in suprabasal keratinocytes through its ability to bind HDACs. Chromatin immunoprecipitation assays demonstrated that, in differentiating cells, E7 acts to inhibit HDAC binding to the E2F2 promoter resulting in activation of expression. Reduction of E2F2 levels through the use of siRNA confirmed that E2F2 expression facilitated HPV replication but its loss did not affect cell proliferation. Our study demonstrates a mechanism by which binding of HDACs to E7 directly modulates viral replication and identifies E2F2 as a possible target for antiviral therapies.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/sj.emboj.7600651</identifier><identifier>PMID: 15861133</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>E2F2 ; E2F2 Transcription Factor ; EMBO09 ; EMBO23 ; Epithelial Cells - enzymology ; Epithelial Cells - virology ; histone deacetylase ; Histone Deacetylases - metabolism ; human papillomavirus ; Humans ; Keratinocytes - enzymology ; Keratinocytes - virology ; Life cycles ; Oncogene Proteins, Viral - metabolism ; Papillomaviridae - enzymology ; Papillomaviridae - genetics ; Papillomavirus E7 Proteins ; Promoter Regions, Genetic ; Proteins ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Transcription, Genetic - physiology ; Up-Regulation</subject><ispartof>The EMBO journal, 2005-05, Vol.24 (10), p.1821-1830</ispartof><rights>European Molecular Biology Organization 2005</rights><rights>Copyright © 2005 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group May 18, 2005</rights><rights>Copyright © 2005, European Molecular Biology Organization 2005 European Molecular Biology Organization</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6041-d01fba6a1cf80e0ebca436ce8e280817a8104f3337c524b838485f4f1d380a403</citedby><cites>FETCH-LOGICAL-c6041-d01fba6a1cf80e0ebca436ce8e280817a8104f3337c524b838485f4f1d380a403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142589/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142589/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,41120,42189,45574,45575,46409,46833,51576,53791,53793</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/sj.emboj.7600651$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15861133$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Longworth, Michelle S</creatorcontrib><creatorcontrib>Wilson, Regina</creatorcontrib><creatorcontrib>Laimins, Laimonis A</creatorcontrib><title>HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>The E7 proteins of human papillomaviruses (HPVs) contribute to oncogenesis by associating with Rb family members as well class I histone deacetylases (HDACs). The binding of HDACs is also important for the maintenance of viral episomes during the differentiation‐dependent productive life cycle. The effects of E7 and other viral proteins on E2F family members were examined in differentiating keratinocytes. E7 was found to specifically activate E2F2 transcription in suprabasal keratinocytes through its ability to bind HDACs. Chromatin immunoprecipitation assays demonstrated that, in differentiating cells, E7 acts to inhibit HDAC binding to the E2F2 promoter resulting in activation of expression. Reduction of E2F2 levels through the use of siRNA confirmed that E2F2 expression facilitated HPV replication but its loss did not affect cell proliferation. Our study demonstrates a mechanism by which binding of HDACs to E7 directly modulates viral replication and identifies E2F2 as a possible target for antiviral therapies.</description><subject>E2F2</subject><subject>E2F2 Transcription Factor</subject><subject>EMBO09</subject><subject>EMBO23</subject><subject>Epithelial Cells - enzymology</subject><subject>Epithelial Cells - virology</subject><subject>histone deacetylase</subject><subject>Histone Deacetylases - metabolism</subject><subject>human papillomavirus</subject><subject>Humans</subject><subject>Keratinocytes - enzymology</subject><subject>Keratinocytes - virology</subject><subject>Life cycles</subject><subject>Oncogene Proteins, Viral - metabolism</subject><subject>Papillomaviridae - enzymology</subject><subject>Papillomaviridae - genetics</subject><subject>Papillomavirus E7 Proteins</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Transcription, Genetic - physiology</subject><subject>Up-Regulation</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFUc9v0zAYtRCIdYU7F5DFYbcUf7HjOBekUdoVtAESA46W4zqtS5oU29nof4-7VO1AQjtZ9vvxPX8PoRdARkCoeONXI7Mu29Uo54TwDB6hATBOkpTk2WM0ICmHhIEoTtCp9ytCSCZyeIpOIBMcgNIBms--fKeAJzmulLa1DSoYj53Z1FarYNsGl1usdLA38dYs8CSdpjg41Xjt7OaOEJau7RZLbIPHtgnG7ejx_daGJZ69Px_7Z-hJpWpvnu_PIfo2nVyPZ8nl54sP4_PLRHPCIJkTqErFFehKEENMqRWjXBthUkEE5EoAYRWlNNdZykpBBRNZxSqYU0EUI3SI3va-m65cm7k2TUxay42za-W2slVW_o00dikX7Y0EYGkmimhwtjdw7a_O-CDX1mtT16oxbeclz-PQAsSDRMh57KFII_H1P8RV27kmbkFCkaWc7moYItKTtGu9d6Y6RAYid0VLv5J3Rct90VHy6v5Xj4J9s5FQ9IRbW5vtg4ZycvXu49Eceq2PsmZh3L3Q_w_0stc0KnTOHAYe8aTHrQ_m9wFW7mfcKs0z-ePThfzKp9djlhN5Rf8AL_fgqA</recordid><startdate>20050518</startdate><enddate>20050518</enddate><creator>Longworth, Michelle S</creator><creator>Wilson, Regina</creator><creator>Laimins, Laimonis A</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>Nature Publishing Group</general><scope>BSCLL</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20050518</creationdate><title>HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs</title><author>Longworth, Michelle S ; Wilson, Regina ; Laimins, Laimonis A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6041-d01fba6a1cf80e0ebca436ce8e280817a8104f3337c524b838485f4f1d380a403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>E2F2</topic><topic>E2F2 Transcription Factor</topic><topic>EMBO09</topic><topic>EMBO23</topic><topic>Epithelial Cells - enzymology</topic><topic>Epithelial Cells - virology</topic><topic>histone deacetylase</topic><topic>Histone Deacetylases - metabolism</topic><topic>human papillomavirus</topic><topic>Humans</topic><topic>Keratinocytes - enzymology</topic><topic>Keratinocytes - virology</topic><topic>Life cycles</topic><topic>Oncogene Proteins, Viral - metabolism</topic><topic>Papillomaviridae - enzymology</topic><topic>Papillomaviridae - genetics</topic><topic>Papillomavirus E7 Proteins</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Transcription, Genetic - physiology</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Longworth, Michelle S</creatorcontrib><creatorcontrib>Wilson, Regina</creatorcontrib><creatorcontrib>Laimins, Laimonis A</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Longworth, Michelle S</au><au>Wilson, Regina</au><au>Laimins, Laimonis A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2005-05-18</date><risdate>2005</risdate><volume>24</volume><issue>10</issue><spage>1821</spage><epage>1830</epage><pages>1821-1830</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>The E7 proteins of human papillomaviruses (HPVs) contribute to oncogenesis by associating with Rb family members as well class I histone deacetylases (HDACs). The binding of HDACs is also important for the maintenance of viral episomes during the differentiation‐dependent productive life cycle. The effects of E7 and other viral proteins on E2F family members were examined in differentiating keratinocytes. E7 was found to specifically activate E2F2 transcription in suprabasal keratinocytes through its ability to bind HDACs. Chromatin immunoprecipitation assays demonstrated that, in differentiating cells, E7 acts to inhibit HDAC binding to the E2F2 promoter resulting in activation of expression. Reduction of E2F2 levels through the use of siRNA confirmed that E2F2 expression facilitated HPV replication but its loss did not affect cell proliferation. Our study demonstrates a mechanism by which binding of HDACs to E7 directly modulates viral replication and identifies E2F2 as a possible target for antiviral therapies.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>15861133</pmid><doi>10.1038/sj.emboj.7600651</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | E2F2 E2F2 Transcription Factor EMBO09 EMBO23 Epithelial Cells - enzymology Epithelial Cells - virology histone deacetylase Histone Deacetylases - metabolism human papillomavirus Humans Keratinocytes - enzymology Keratinocytes - virology Life cycles Oncogene Proteins, Viral - metabolism Papillomaviridae - enzymology Papillomaviridae - genetics Papillomavirus E7 Proteins Promoter Regions, Genetic Proteins Transcription Factors - biosynthesis Transcription Factors - genetics Transcription, Genetic - physiology Up-Regulation |
title | HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs |
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