PMID:22190036

Citation	Zhang, W, Du, J, Evans, SL, Yu, Y and Yu, XF (2012) T-cell differentiation factor CBF-β regulates HIV-1 Vif-mediated evasion of host restriction. Nature 481:376-9
Abstract	The human APOBEC3 cytidine deaminases are potent inhibitors of diverse retroviruses, including human immunodeficiency virus-1 (HIV-1). HIV-1 Vif forms an E3 ubiquitin ligase complex with cullin 5 (CUL5), elongin B and elongin C , which promotes the polyubiquitination and degradation of APOBEC3 substrates. Here we demonstrate in human T cells that core binding factor β (CBF-β) is a key regulator of the evasion of HIV-1 from the host defence mediated by APOBEC3. CBF-β, the non-DNA-binding subunit of a heterodimeric transcription factor, regulates the folding and DNA-binding activity of partner RUNX family proteins, which have important roles in the development and differentiation of diverse cell types, including T lymphocytes. In our study, knockdown of endogenous CBF-β blocked Vif-induced APOBEC3G polyubiquitination and degradation. CBF-β was not required for the interaction between Vif and APOBEC3G, yet was essential for the assembly of the Vif-CUL5 E3-ubiquitin-ligase complex. CBF-β proved to be a unique regulator of primate lentiviral Vif and not a general component of the CUL5 E3 ubiquitin ligase. We show that Vif and CBF-β physically interact, and that the amino-terminal region of Vif is required for this interaction. Furthermore, interactions with Vif required regions in CBF-β that are not involved in RUNX protein binding. Considering the importance of the interaction between Vif and CBF-β, disrupting this interaction represents an attractive pharmacological intervention against HIV-1.
Links	PubMed Online version:10.1038/nature10718
Keywords	Cell Differentiation; Cell Line; Core Binding Factor alpha Subunits/metabolism; Core Binding Factor beta Subunit/chemistry; Core Binding Factor beta Subunit/deficiency; Core Binding Factor beta Subunit/genetics; Core Binding Factor beta Subunit/metabolism; Cullin Proteins/metabolism; Cytidine Deaminase/genetics; Cytidine Deaminase/metabolism; Gene Knockdown Techniques; HEK293 Cells; HIV-1/genetics; HIV-1/immunology; HIV-1/physiology; Host-Pathogen Interactions; Humans; Immune Evasion; Immunoprecipitation; Models, Molecular; Protein Binding; Proteolysis; T-Lymphocytes/cytology; T-Lymphocytes/immunology; Ubiquitin-Protein Ligases/metabolism; Ubiquitination; vif Gene Products, Human Immunodeficiency Virus/chemistry; vif Gene Products, Human Immunodeficiency Virus/genetics; vif Gene Products, Human Immunodeficiency Virus/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PEBB		GO:0000209: protein polyubiquitination	ECO:0000315:		P		Figure 4 indicates CBF-β's role in APOBEC3G ubiquitination	complete CACAO 5212
HUMAN:PEBB	involved_in	GO:0000209: protein polyubiquitination	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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