Core Binding Factor Beta Plays a Critical Role by Facilitating the Assembly of the Vif-Cullin 5 E3 Ubiquitin Ligase

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 (CBF beta). In this study, we investigated the Vif-CBF beta interaction and the role of CBF beta in the E3 ligase assembly. Vif-CBF beta interaction requires an extensive region of Vif spanning most of its amino terminus and zinc finger region, and cullin 5 (Cu15) binding enhances the stability of the Vif-CBF beta interaction. Our results further demonstrate that CBF beta plays a critical role in facilitating Cu15 binding to the Vif/elongin B/elongin C complex. Vif, with or without bound substrate, is unable to bind Cu15 in the absence of CBF beta. These studies support the notion that CBF beta serves as a molecular chaperone to facilitate Vif-E3 ligase assembly.