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Title: HIV-1 viral infectivity factor interacts with TP53 to induce G2 cell cycle arrest and positively regulate viral replication
Authors: Izumi, Taisuke
Io, Katsuhiro
Matsui, Masashi
Shirakawa, Kotaro  kyouindb  KAKEN_id
Shinohara, Masanobu
Nagai, Yuya
Kawahara, Masahiro  KAKEN_id
Kobayashi, Masayuki  KAKEN_id
Kondoh, Hiroshi
Misawa, Naoko
Koyanagi, Yoshio  kyouindb  KAKEN_id
Uchiyama, Takashi
Takaori-Kondo, Akifumi
Author's alias: 高折, 晃史
Keywords: AIDS
Issue Date: 11-Nov-2010
Publisher: The National Academy of Sciences
Journal title: Proceedings of the National Academy of Sciences
Abstract: Viral 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.
Description: HIV-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.
Rights: ©2010 by the National Academy of Sciences
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.
DOI(Published Version): 10.1073/pnas.1008076107
PubMed ID: 21071676
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