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HIV type 1 viral infectivity factor and the RUNX transcription factors interact with core binding factor ? on genetically distinct surfaces.


ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) requires the cellular transcription factor core binding factor subunit ? (CBF?) to stabilize its viral infectivity factor (Vif) protein and neutralize the APOBEC3 restriction factors. CBF? normally heterodimerizes with the RUNX family of transcription factors, enhancing their stability and DNA-binding affinity. To test the hypothesis that Vif may act as a RUNX mimic to bind CBF?, we generated a series of CBF? mutants at the RUNX/CBF? interface and tested their ability to stabilize Vif and impact transcription at a RUNX-dependent promoter. While several CBF? amino acid substitutions disrupted promoter activity, none of these impacted the ability of CBF? to stabilize Vif or enhance degradation of APOBEC3G. A mutagenesis screen of CBF? surface residues identified a single amino acid change, F68D, that disrupted Vif binding and its ability to degrade APOBEC3G. This mutant still bound RUNX and stimulated RUNX-dependent transcription. These separation-of-function mutants demonstrate that HIV-1 Vif and the RUNX transcription factors interact with cellular CBF? on genetically distinct surfaces.

SUBMITTER: Hultquist JF 

PROVIDER: S-EPMC3505047 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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HIV type 1 viral infectivity factor and the RUNX transcription factors interact with core binding factor β on genetically distinct surfaces.

Hultquist Judd F JF   McDougle Rebecca M RM   Anderson Brett D BD   Harris Reuben S RS  

AIDS research and human retroviruses 20120813 12


Human immunodeficiency virus type 1 (HIV-1) requires the cellular transcription factor core binding factor subunit β (CBFβ) to stabilize its viral infectivity factor (Vif) protein and neutralize the APOBEC3 restriction factors. CBFβ normally heterodimerizes with the RUNX family of transcription factors, enhancing their stability and DNA-binding affinity. To test the hypothesis that Vif may act as a RUNX mimic to bind CBFβ, we generated a series of CBFβ mutants at the RUNX/CBFβ interface and test  ...[more]

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