Induction of APOBEC3G Ubiquitination and Degradation by an HIV-1 Vif-Cul5-SCF Complex

American Association for the Advancement of Science (AAAS) - Tập 302 Số 5647 - Trang 1056-1060 - 2003
Xianghui Yu1,2,3, Yunkai Yu1,2,3, Bindong Liu1,2,3, Kun Luo1,2,3, Wei Kong1,2,3, Panyong Mao1,2,3, Xiao-Fang Yu1,2,3
1Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA,
2Jilin University, Jilin, People's Republic of China.
3Zhejiang University, Zhejiang, People’s Republic of China

Tóm tắt

Human immunodeficiency virus–1 (HIV-1) Vif is essential for viral evasion of host antiviral factor CEM15/APOBEC3G. We report that Vif interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an Skp1-cullin-F-box (SCF)–like complex. The ability of Vif to suppress antiviral activity of APOBEC3G was specifically dependent on Cul5-SCF function, allowing Vif to interact with APOBEC3G and induce its ubiquitination and degradation. A Vif mutant that interacted with APOBEC3G but not with Cul5-SCF was functionally inactive. The Cul5-SCF was also required for Vif function in distantly related simian immunodeficiency virus mac. These results indicate that the conserved Cul5-SCF pathway used by Vif is a potential target for antiviral development.

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We thank R. Garten T. Sarkis R. Markham M. Dettenhofer and C. Pickart for advice and technical assistance and D. McClellan for editorial assistance. The following reagents were obtained through the Acquired Immunodifficiency Syndrome (AIDS) Research Reagents Program Division of AIDS National Institute of Allergy and Infectious Diseases NIH: antiserum to HIV-1 Vif (Cat. #2221). Protein identification was performed in the AB Mass Spectrometry/Proteomics Facility at Johns Hopkins School of Medicine with support from National Center for Research Resources shared instrumentation grant 1S10-RR14702 the Johns Hopkins Fund for Medical Discovery and the Institute for Cell Engineering.

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American Association for the Advancement of Science (AAAS)

Tập 302 Số 5647

1056-1060

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