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Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2

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dc.contributor.authorLiang, Xiaozhen-
dc.contributor.authorPickering, Mary T.-
dc.contributor.authorCho, Nam-Hyuk-
dc.contributor.authorChang, Heesoon-
dc.contributor.authorVolkert, Michael R.-
dc.contributor.authorKowalik, Timothy F.-
dc.contributor.authorJung, Jae U.-
dc.date.accessioned2010-01-12T02:19:15Z-
dc.date.available2010-01-12T02:19:15Z-
dc.date.issued2006-05-30-
dc.identifier.citationJ Virol. 2006 Jun;80(12):5862-74.en
dc.identifier.issn0022-538X (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16731925-
dc.identifier.urihttps://hdl.handle.net/10371/29589-
dc.description.abstractInfected cells recognize viral replication as a DNA damage stress and elicit a DNA damage response that ultimately induces apoptosis as part of host immune surveillance. Here, we demonstrate a novel mechanism where the murine gamma herpesvirus 68 (gammaHV68) latency-associated, anti-interferon M2 protein inhibits DNA damage-induced apoptosis by interacting with the DDB1/COP9/cullin repair complex and the ATM DNA damage signal transducer. M2 expression constitutively induced DDB1 nuclear localization and ATM kinase activation in the absence of DNA damage. Activated ATM subsequently induced Chk activation and p53 phosphorylation and stabilization without eliciting H2AX phosphorylation and MRN recruitment to foci upon DNA damage. Consequently, M2 expression inhibited DNA repair, rendered cells resistant to DNA damage-induced apoptosis, and induced a G(1) cell cycle arrest. Our results suggest that gammaHV68 M2 blocks apoptosis-mediated intracellular innate immunity, which might ultimately contribute to its role in latent infection.en
dc.language.isoen-
dc.publisherAmerican Society for Microbiologyen
dc.subjectActive Transport, Cell Nucleusen
dc.subjectAnimalsen
dc.subjectApoptosisen
dc.subjectCell Cycleen
dc.subjectCell Lineen
dc.subjectDNA Repairen
dc.subjectDNA-Binding Proteins/metabolismen
dc.subjectG1 Phaseen
dc.subjectHerpesviridae Infectionsen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectRhadinovirus/*physiologyen
dc.subjectTumor Virus Infectionsen
dc.subjectViral Matrix Proteins/*physiologyen
dc.subjectDNA Damage-
dc.subjectSignal Transduction-
dc.subjectVirus Latency-
dc.titleDeregulation of DNA damage signal transduction by herpesvirus latency-associated M2en
dc.typeArticleen
dc.contributor.AlternativeAuthor조남혁-
dc.contributor.AlternativeAuthor장희순-
dc.contributor.AlternativeAuthor정재유-
dc.identifier.doi10.1128/JVI.02732-05-
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