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dc.contributor.authorMarcos-Villar, Laura-
dc.contributor.authorLopitz-Otsoa, Fernando-
dc.contributor.authorGallego, Pedro-
dc.contributor.authorMuñoz-Fontela, César-
dc.contributor.authorGonzález-Santamaría, José-
dc.contributor.authorCampagna, Michela-
dc.contributor.authorShou-Jiang, Gao-
dc.contributor.authorS. Rodríguez, Manuel-
dc.contributor.authorRivas, Carmen-
dc.identifier.citationJournal of Virology 83(17): 8849-8858 (2009)en_US
dc.description10 pages, 7 figs, supplementary information may be found at http://jvi.asm.org/en_US
dc.description.abstractInfection by herpesviruses causes a dramatic disturbance of PML Oncogenic Domains (PODs) that has been suggested to be essential for viral lytic replication. Several proteins from Kaposi’s sarcoma-associated herpesvirus (KSHV) have been tested as putative PODs disrupting factors with negative results. Here, we show that LANA2, a viral protein that is absolutely required for the viability and proliferation of KSHV-infected primary effusion lymphoma (PEL) cells, increases the levels of SUMO2-ubiquitin-modified PML and induces the disruption of PODs by a proteasome-mediated mechanism. In addition, we demonstrate that this disruption is largely dependent both on the integrity of a SUMO-interaction motif in LANA2 and on the lysine 160 from PML. Moreover, silencing of the LANA2 expression in PEL cells by RNA interference led to an increase in the PML levels. Finally, we demonstrate that LANA2 relieves PML-mediated transcriptional repression of survivin, a protein that directly contributes to malignant progression of PEL. This represents the first example of inactivation of these important antiviral structures by KSHV.en_US
dc.description.sponsorshipLMV is supported by Comunidad de Madrid. MC is supported by Fundación Botín. JG-S is supported by the IFARHU-SENACYT Program from Panama. PG is funded by the JAE CSIC Program. MSR and FLO are funded by the Ministerio de Educación y Ciencia grant BFU 2005-04091, Fondo de Investigaciones Sanitarias, CIBERhed. CR is funded by Spanish Ministry of Education and Science (BIO2005-00599) and Fundación de Investigación Médica Mútua Madrileña.en_US
dc.format.extent1722480 bytes-
dc.publisherAmerican Society for Microbiologyen_US
dc.titleKaposi's sarcoma-associated herpesvirus protein LANA2 disrupts PML oncogenic domains and inhibits PML-mediated transcriptional repression of the survivin geneen_US
dc.description.peerreviewedPeer revieweden_US
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