Biology of the adenovirus E4orf4 protein: from virus infection to cancer cell death.
Identifieur interne : 000142 ( Main/Exploration ); précédent : 000141; suivant : 000143Biology of the adenovirus E4orf4 protein: from virus infection to cancer cell death.
Auteurs : Tamar Kleinberger [Israël]Source :
- FEBS letters [ 1873-3468 ] ; 2020.
Abstract
The adenovirus (Ad) early region 4 open reading frame 4 (E4orf4) protein is a small 14-kDa polypeptide endowed with important viral regulatory functions. Although deletion of E4orf4 does not have a major effect on Ad replication due to redundancy among many Ad proteins, E4orf4 provides several functions that improve viral replication. E4orf4 contributes to temporal regulation of virus infection by downregulating early viral gene expression and by altering splicing patterns of Ad mRNAs. It also optimizes the cellular environment for Ad replication by activating the mammalian target of rapamycin pathway to increase viral protein production and by impacting the cell cycle. In addition, E4orf4 participates in the inhibition of the host DNA damage response, promoting the ability of Ad to counteract this antiviral defense mechanism. To fulfill these functions, E4orf4 interacts with numerous cellular proteins, including the major E4orf4 partner, protein phosphatase 2A (PP2A). When expressed alone, outside the context of virus infection, E4orf4 induces an evolutionarily conserved, caspase-independent, cancer-selective cell death with many interesting characteristics. This review critically describes E4orf4's contribution to Ad infection and cancer-cell death.
DOI: 10.1002/1873-3468.13704
PubMed: 31792953
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Biology of the adenovirus E4orf4 protein: from virus infection to cancer cell death.</title><author><name sortKey="Kleinberger, Tamar" sort="Kleinberger, Tamar" uniqKey="Kleinberger T" first="Tamar" last="Kleinberger">Tamar Kleinberger</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Microbiology, the Rappaport Faculty of Medicine, Technion -Israel Institute of Technology, Haifa, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Department of Molecular Microbiology, the Rappaport Faculty of Medicine, Technion -Israel Institute of Technology, Haifa</wicri:regionArea><wicri:noRegion>Haifa</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:31792953</idno><idno type="pmid">31792953</idno><idno type="doi">10.1002/1873-3468.13704</idno><idno type="wicri:Area/Main/Corpus">000151</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000151</idno><idno type="wicri:Area/Main/Curation">000151</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000151</idno><idno type="wicri:Area/Main/Exploration">000151</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Biology of the adenovirus E4orf4 protein: from virus infection to cancer cell death.</title><author><name sortKey="Kleinberger, Tamar" sort="Kleinberger, Tamar" uniqKey="Kleinberger T" first="Tamar" last="Kleinberger">Tamar Kleinberger</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Microbiology, the Rappaport Faculty of Medicine, Technion -Israel Institute of Technology, Haifa, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Department of Molecular Microbiology, the Rappaport Faculty of Medicine, Technion -Israel Institute of Technology, Haifa</wicri:regionArea><wicri:noRegion>Haifa</wicri:noRegion></affiliation></author></analytic><series><title level="j">FEBS letters</title><idno type="eISSN">1873-3468</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The adenovirus (Ad) early region 4 open reading frame 4 (E4orf4) protein is a small 14-kDa polypeptide endowed with important viral regulatory functions. Although deletion of E4orf4 does not have a major effect on Ad replication due to redundancy among many Ad proteins, E4orf4 provides several functions that improve viral replication. E4orf4 contributes to temporal regulation of virus infection by downregulating early viral gene expression and by altering splicing patterns of Ad mRNAs. It also optimizes the cellular environment for Ad replication by activating the mammalian target of rapamycin pathway to increase viral protein production and by impacting the cell cycle. In addition, E4orf4 participates in the inhibition of the host DNA damage response, promoting the ability of Ad to counteract this antiviral defense mechanism. To fulfill these functions, E4orf4 interacts with numerous cellular proteins, including the major E4orf4 partner, protein phosphatase 2A (PP2A). When expressed alone, outside the context of virus infection, E4orf4 induces an evolutionarily conserved, caspase-independent, cancer-selective cell death with many interesting characteristics. This review critically describes E4orf4's contribution to Ad infection and cancer-cell death.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">31792953</PMID><DateRevised><Year>2020</Year><Month>06</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-3468</ISSN><JournalIssue CitedMedium="Internet"><Volume>594</Volume><Issue>12</Issue><PubDate><Year>2020</Year><Month>Jun</Month></PubDate></JournalIssue><Title>FEBS letters</Title><ISOAbbreviation>FEBS Lett</ISOAbbreviation></Journal><ArticleTitle>Biology of the adenovirus E4orf4 protein: from virus infection to cancer cell death.</ArticleTitle><Pagination><MedlinePgn>1891-1917</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/1873-3468.13704</ELocationID><Abstract><AbstractText>The adenovirus (Ad) early region 4 open reading frame 4 (E4orf4) protein is a small 14-kDa polypeptide endowed with important viral regulatory functions. Although deletion of E4orf4 does not have a major effect on Ad replication due to redundancy among many Ad proteins, E4orf4 provides several functions that improve viral replication. E4orf4 contributes to temporal regulation of virus infection by downregulating early viral gene expression and by altering splicing patterns of Ad mRNAs. It also optimizes the cellular environment for Ad replication by activating the mammalian target of rapamycin pathway to increase viral protein production and by impacting the cell cycle. In addition, E4orf4 participates in the inhibition of the host DNA damage response, promoting the ability of Ad to counteract this antiviral defense mechanism. To fulfill these functions, E4orf4 interacts with numerous cellular proteins, including the major E4orf4 partner, protein phosphatase 2A (PP2A). When expressed alone, outside the context of virus infection, E4orf4 induces an evolutionarily conserved, caspase-independent, cancer-selective cell death with many interesting characteristics. This review critically describes E4orf4's contribution to Ad infection and cancer-cell death.</AbstractText><CopyrightInformation>© 2019 Federation of European Biochemical Societies.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kleinberger</LastName><ForeName>Tamar</ForeName><Initials>T</Initials><Identifier Source="ORCID">https://orcid.org/0000-0002-0300-8679</Identifier><AffiliationInfo><Affiliation>Department of Molecular Microbiology, the Rappaport Faculty of Medicine, Technion -Israel Institute of Technology, Haifa, Israel.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>2013140</GrantID><Agency>United States-Israel Binational Science Foundation</Agency><Country></Country></Grant><Grant><GrantID>261/15</GrantID><Agency>Israel Science Foundation</Agency><Country></Country></Grant><Grant><GrantID>20150008</GrantID><Agency>Israel Cancer Association</Agency><Country></Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>12</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>FEBS Lett</MedlineTA><NlmUniqueID>0155157</NlmUniqueID><ISSNLinking>0014-5793</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">DNA damage response</Keyword><Keyword MajorTopicYN="N">E4orf4</Keyword><Keyword MajorTopicYN="N">PP2A</Keyword><Keyword MajorTopicYN="N">RNA splicing</Keyword><Keyword MajorTopicYN="N">Src</Keyword><Keyword MajorTopicYN="N">adenovirus</Keyword><Keyword MajorTopicYN="N">cancer-cell death</Keyword><Keyword MajorTopicYN="N">cell cycle</Keyword><Keyword MajorTopicYN="N">chromatin remodeling</Keyword><Keyword MajorTopicYN="N">virus-host cell interactions</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>11</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>11</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>11</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>12</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>12</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>12</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31792953</ArticleId><ArticleId IdType="doi">10.1002/1873-3468.13704</ArticleId></ArticleIdList><ReferenceList><Title>References</Title><Reference><Citation>Zhao H, Chen M and Pettersson U (2014) A new look at adenovirus splicing. 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