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CBFb Stabilizes HIV Vif to Counteract APOBEC3 at the Expense of RUNX1 Target Gene Expression [gene expression]

ABSTRACT: The HIV-1 accessory protein Vif hijacks a cellular Cullin-RING ubiquitin ligase, CRL5, to promote degradation of the APOBEC3 (A3) family of restriction factors. Recently, the cellular transcription cofactor CBFb was shown to form a complex with CRL5-Vif and to be essential for A3 degradation and viral infectivity. We now demonstrate that CBFb is required for assembling a well-ordered CRL5-Vif complex by inhibiting Vif oligomerization and by activating CRL5-Vif via direct interaction. The CRL5-Vif-CBFb holoenzyme forms a welldeﬁned heterohexamer, indicating that Vif simultaneously hijacks CRL5 and CBFb. Heterodimers of CBFb and RUNX transcription factors contribute toward the regulation of genes, including those with immune system functions. We show that binding of Vif to CBFb is mutually exclusive with RUNX heterodimerization and impacts the expression of genes whose regulatory domains are associated with RUNX1. Our results provide a mechanism by which a pathogen with limited coding capacity uses one factor to hijack multiple host pathways.

ORGANISM(S): Homo sapiens

PROVIDER: GSE42574 | GEO | 2013/01/17

SECONDARY ACCESSION(S): PRJNA182317

REPOSITORIES: GEO

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CBFb Stabilizes HIV Vif to Counteract APOBEC3 at the Expense of RUNX1 Target Gene Expression [ChIP-seq]

Project description:The HIV-1 accessory protein Vif hijacks a cellular Cullin-RING ubiquitin ligase, CRL5, to promote degradation of the APOBEC3 (A3) family of restriction factors. Recently, the cellular transcription cofactor CBFb was shown to form a complex with CRL5-Vif and to be essential for A3 degradation and viral infectivity. We now demonstrate that CBFb is required for assembling a well-ordered CRL5-Vif complex by inhibiting Vif oligomerization and by activating CRL5-Vif via direct interaction. The CRL5-Vif-CBFb holoenzyme forms a welldeﬁned heterohexamer, indicating that Vif simultaneously hijacks CRL5 and CBFb. Heterodimers of CBFb and RUNX transcription factors contribute toward the regulation of genes, including those with immune system functions. We show that binding of Vif to CBFb is mutually exclusive with RUNX heterodimerization and impacts the expression of genes whose regulatory domains are associated with RUNX1. Our results provide a mechanism by which a pathogen with limited coding capacity uses one factor to hijack multiple host pathways. Identification of RUNX1 binding sites in the Jurkat cell line

2013-01-17 | E-GEOD-42575 | biostudies-arrayexpress

CBFb Stabilizes HIV Vif to Counteract APOBEC3 at the Expense of RUNX1 Target Gene Expression [gene expression]

Project description:The HIV-1 accessory protein Vif hijacks a cellular Cullin-RING ubiquitin ligase, CRL5, to promote degradation of the APOBEC3 (A3) family of restriction factors. Recently, the cellular transcription cofactor CBFb was shown to form a complex with CRL5-Vif and to be essential for A3 degradation and viral infectivity. We now demonstrate that CBFb is required for assembling a well-ordered CRL5-Vif complex by inhibiting Vif oligomerization and by activating CRL5-Vif via direct interaction. The CRL5-Vif-CBFb holoenzyme forms a wellde?ned heterohexamer, indicating that Vif simultaneously hijacks CRL5 and CBFb. Heterodimers of CBFb and RUNX transcription factors contribute toward the regulation of genes, including those with immune system functions. We show that binding of Vif to CBFb is mutually exclusive with RUNX heterodimerization and impacts the expression of genes whose regulatory domains are associated with RUNX1. Our results provide a mechanism by which a pathogen with limited coding capacity uses one factor to hijack multiple host pathways. Analysis of Vif-dependent effects on gene expression in Jurkats when cells are activated for 4 or 6 hours with PMA and PHA

2013-01-17 | E-GEOD-42574 | biostudies-arrayexpress

CBFb Stabilizes HIV Vif to Counteract APOBEC3 at the Expense of RUNX1 Target Gene Expression [ChIP-seq]

2013-01-17 | GSE42575 | GEO

Gene expression analysis of Cbfb-deficient LSK and GMP

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Gene expression analysis of Cbfb-deficient LSK and GMP

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2014-04-05 | E-GEOD-55227 | biostudies-arrayexpress

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2010-04-12 | E-GEOD-19194 | biostudies-arrayexpress

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CBFb Stabilizes HIV Vif to Counteract APOBEC3 at the Expense of RUNX1 Target Gene Expression

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-01-17 | E-GEOD-42576 | biostudies-arrayexpress