MDM2 is a Novel E3 Ligase for HIV-1 Vif

Overview

Journal Retrovirology

Publisher Biomed Central

Specialty Microbiology

Date 2009 Jan 9

PMID 19128510

Citations 39

Authors

Taisuke Izumi

Akifumi Takaori-Kondo

Kotaro Shirakawa

Hiroaki Higashitsuji

Katsuhiko Itoh

Katsuhiro Io

Masashi Matsui

Kazuhiro Iwai

Hiroshi Kondoh

Toshihiro Sato

Mitsunori Tomonaga

Satoru Ikeda

Hirofumi Akari

Yoshio Koyanagi

Jun Fujita

Takashi Uchiyama

Affiliations

Soon will be listed here.

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.

Citing Articles

Human microRNA miR-197-3p positively regulates HIV-1 virion infectivity through its target DDX52 by stabilizing Vif protein expression.

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PMID: 39826696 PMC: 11867528. DOI: 10.1016/j.jbc.2025.108198.

Interactions between HIV proteins and host restriction factors: implications for potential therapeutic intervention in HIV infection.

Rashid F, Zaongo S, Iqbal H, Harypursat V, Song F, Chen Y Front Immunol. 2024; 15:1390650.

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Help or Hinder: Protein Host Factors That Impact HIV-1 Replication.

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Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein Represses Cellular MDM2 Expression via Suppressing the Sp1- and p53-Mediated Transactivation.

Lin C, Wang S, Hung C, Chang P, Chen L Int J Mol Sci. 2022; 23(15).

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Human Immunodeficiency Virus Type 1 Vif Up-Regulates the Expression of Tat AKT Signaling Pathway: Role of Ubiquitin Specific Protease 17.

Lata S, Sood V, Banerjea A Front Microbiol. 2022; 13:828430.

PMID: 35387085 PMC: 8978020. DOI: 10.3389/fmicb.2022.828430.

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