Core binding factor beta plays a critical role by facilitating the assembly of the Vif-Cullin 5 E3 ubiquitin ligase

Jennifer L. Fribourgh, Henry C. Nguyen, Leslie S. Wolfe, David C. DeWitt, Wenyan Zhang, Xiao Fang Yu, Elizabeth Rhoades, Yong Xiong

Research output: Contribution to journalArticle

Abstract

The HIV-1 virion infectivity factor (Vif) targets the cellular cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) for degradation via the host ubiquitin-proteasome pathway. Vif recruits a cellular E3 ubiquitin ligase to polyubiquitinate A3G/F. The activity of Vif critically depends on the cellular core binding factor beta (CBFβ). In this study, we investigated the Vif-CBFβ interaction and the role of CBFβ in the E3 ligase assembly. Vif-CBFβ interaction requires an extensive region of Vif spanning most of its amino terminus and zinc finger region, and cullin 5 (Cul5) binding enhances the stability of the Vif-CBFβ interaction. Our results further demonstrate that CBFβ plays a critical role in facilitating Cul5 binding to the Vif/elongin B/elongin C complex. Vif, with or without bound substrate, is unable to bind Cul5 in the absence of CBFβ. These studies support the notion that CBFβ serves as a molecular chaperone to facilitate Vif-E3 ligase assembly.

Original languageEnglish (US)
Pages (from-to)3309-3319
Number of pages11
JournalJournal of Virology
Volume88
Issue number6
DOIs
StatePublished - 2014

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Core Binding Factor beta Subunit
Cullin Proteins
ubiquitin-protein ligase
Ubiquitin-Protein Ligases
virion
Virion
pathogenicity
ligases
Cytidine Deaminase
molecular chaperones
Molecular Chaperones
zinc finger motif
Zinc Fingers
proteasome endopeptidase complex
Proteasome Endopeptidase Complex
ubiquitin
Ubiquitin
Human immunodeficiency virus 1

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Fribourgh, J. L., Nguyen, H. C., Wolfe, L. S., DeWitt, D. C., Zhang, W., Yu, X. F., ... Xiong, Y. (2014). Core binding factor beta plays a critical role by facilitating the assembly of the Vif-Cullin 5 E3 ubiquitin ligase. Journal of Virology, 88(6), 3309-3319. https://doi.org/10.1128/JVI.03824-13

Core binding factor beta plays a critical role by facilitating the assembly of the Vif-Cullin 5 E3 ubiquitin ligase. / Fribourgh, Jennifer L.; Nguyen, Henry C.; Wolfe, Leslie S.; DeWitt, David C.; Zhang, Wenyan; Yu, Xiao Fang; Rhoades, Elizabeth; Xiong, Yong.

In: Journal of Virology, Vol. 88, No. 6, 2014, p. 3309-3319.

Research output: Contribution to journalArticle

Fribourgh, JL, Nguyen, HC, Wolfe, LS, DeWitt, DC, Zhang, W, Yu, XF, Rhoades, E & Xiong, Y 2014, 'Core binding factor beta plays a critical role by facilitating the assembly of the Vif-Cullin 5 E3 ubiquitin ligase', Journal of Virology, vol. 88, no. 6, pp. 3309-3319. https://doi.org/10.1128/JVI.03824-13
Fribourgh, Jennifer L. ; Nguyen, Henry C. ; Wolfe, Leslie S. ; DeWitt, David C. ; Zhang, Wenyan ; Yu, Xiao Fang ; Rhoades, Elizabeth ; Xiong, Yong. / Core binding factor beta plays a critical role by facilitating the assembly of the Vif-Cullin 5 E3 ubiquitin ligase. In: Journal of Virology. 2014 ; Vol. 88, No. 6. pp. 3309-3319.
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