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Induction of APOBEC3G Ubiquitination and Degradation by an HIV-1 Vif-Cul5-SCF Complex
Abstract
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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Cites
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
Mangeat, B., Turelli, P., Caron, G., Friedli, M., Perrin, L., & Trono, D. (2003) · Nature · doi:10.1038/nature01709 · Cited by 1,486
Cited by
Ubiquitin ligases: structure, function, and regulation
Zheng, N., & Shabek, N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014922 · Cited by 1,499
Duda, D. M., Borg, L. A., Scott, D. C., Hunt, H. W., Hammel, M., & Schulman, B. A. (2008) · Cell · doi:10.1016/j.cell.2008.07.022 · Cited by 767
Harris, R. S., & Dudley, J. P. (2015) · Virology · doi:10.1016/j.virol.2015.03.012 · Cited by 551
Rules of engagement: molecular insights from host–virus arms races
Daugherty, M. D., & Malik, H. S. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155522 · Cited by 515
Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G
Sawyer, S. L., Emerman, M., & Malik, H. S. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020275 · Cited by 485
Metadata
- Authors
- Yu, X., Yu, Y., Liu, B., Luo, K., Kong, W., Mao, P., & Yu, X.-F.
- Venue
- Science
- Published
- 2003-11-07
- Volume
- 302
- Issue
- 5647
- Pages
- 1056-1060
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2042486230
- Cited by
- 1,200
- References
- 1
- FWCI
- 22.51
- Type
- journal article
- Language
- en
- Open access
- closed
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- Yu, X., Yu, Y., Liu, B., Luo, K., Kong, W., Mao, P., & Yu, X.-F. (2003). Induction of APOBEC3G Ubiquitination and Degradation by an HIV-1 Vif-Cul5-SCF Complex. Science. https://doi.org/10.1126/science.1089591
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