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dc.contributor.authorIzumi, Taisukeja
dc.contributor.authorIo, Katsuhiroja
dc.contributor.authorMatsui, Masashija
dc.contributor.authorShirakawa, Kotaroja
dc.contributor.authorShinohara, Masanobuja
dc.contributor.authorNagai, Yuyaja
dc.contributor.authorKawahara, Masahiroja
dc.contributor.authorKobayashi, Masayukija
dc.contributor.authorKondoh, Hiroshija
dc.contributor.authorMisawa, Naokoja
dc.contributor.authorKoyanagi, Yoshioja
dc.contributor.authorUchiyama, Takashija
dc.contributor.authorTakaori-Kondo, Akifumija
dc.contributor.alternative高折, 晃史ja
dc.descriptionHIV-1ウイルスのVif蛋白による新たなHIV-1ウイルス複製制御メカニズムの解明. 京都大学プレスリリース. 2010-11-09.ja
dc.description.abstractViral infectivity factor, an accessory protein encoded in the HIV-1 genome, induces G2 cell cycle arrest; however, the biological significance and mechanism(s) remain totally unclear. Here we demonstrate that the TP53 pathway is involved in Vif-mediated G2 cell cycle arrest. Vif enhances the stability and transcriptional activity of TP53 by blocking the MDM2-mediated ubiquitination and nuclear export of TP53. Furthermore, Vif causes G2 cell cycle arrest in a TP53-dependent manner. HXB2 Vif lacks these activities toward TP53 and cannot induce G2 cell cycle arrest. Using mutagenesis, we demonstrate that the critical residues for this function are located in the N-terminal region of Vif. Finally, we construct a mutant NL4-3 virus with an NL4-3/HXB2 chimeric Vif defective for the ability to induce cell cycle arrest and show that the mutant virus replicates less effectively than the wild-type NL4-3 virus in T cells expressing TP53. These data imply that Vif induces G2 cell cycle arrest through functional interaction with the TP53/MDM2 axis and that the G2 cell cycle arrest induced by Vif has a positive effect on HIV-1 replication. This report demonstrates the molecular mechanisms and the biological significance of Vif-mediated G2 cell cycle arrest for HIV-1 infection.ja
dc.publisherThe National Academy of Sciencesja
dc.rights©2010 by the National Academy of Sciencesja
dc.rightsこの論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。This is not the published version. Please cite only the published version.ja
dc.titleHIV-1 viral infectivity factor interacts with TP53 to induce G2 cell cycle arrest and positively regulate viral replicationja
dc.type.niitypeJournal Articleja
dc.identifier.jtitleProceedings of the National Academy of Sciencesja
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