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Title: MDM2 is a novel E3 ligase for HIV-1 Vif.
Authors: Izumi, Taisuke
Takaori-Kondo, Akifumi
Shirakawa, Kotaro  kyouindb  KAKEN_id
Higashitsuji, Hiroaki  kyouindb  KAKEN_id
Itoh, Katsuhiko  kyouindb  KAKEN_id
Io, Katsuhiro
Matsui, Masashi
Iwai, Kazuhiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Kondoh, Hiroshi  kyouindb  KAKEN_id
Sato, Toshihiro
Tomonaga, Mitsunori
Ikeda, Satoru  KAKEN_id
Akari, Hirofumi  kyouindb  KAKEN_id  orcid (unconfirmed)
Koyanagi, Yoshio  kyouindb  KAKEN_id
Fujita, Jun  KAKEN_id
Uchiyama, Takashi
Author's alias: 高折, 晃史
Issue Date: 7-Jan-2009
Publisher: BioMed Central Ltd.
Journal title: Retrovirology
Volume: 6
Thesis number: 1
Abstract: The human immunodeficiency virus type 1 (HIV-1) Vif plays a crucial role in the viral life cycle by antagonizing a host restriction factor APOBEC3G (A3G). Vif interacts with A3G and induces its polyubiquitination and subsequent degradation via the formation of active ubiquitin ligase (E3) complex with Cullin5-ElonginB/C. Although Vif itself is also ubiquitinated and degraded rapidly in infected cells, precise roles and mechanisms of Vif ubiquitination are largely unknown. Here we report that MDM2, known as an E3 ligase for p53, is a novel E3 ligase for Vif and induces polyubiquitination and degradation of Vif. We also show the mechanisms by which MDM2 only targets Vif, but not A3G that binds to Vif. MDM2 reduces cellular Vif levels and reversely increases A3G levels, because the interaction between MDM2 and Vif precludes A3G from binding to Vif. Furthermore, we demonstrate that MDM2 negatively regulates HIV-1 replication in non-permissive target cells through Vif degradation. These data suggest that MDM2 is a regulator of HIV-1 replication and might be a novel therapeutic target for anti-HIV-1 drug.
Rights: © 2009 Izumi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI(Published Version): 10.1186/1742-4690-6-1
PubMed ID: 19128510
Appears in Collections:Journal Articles

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