|
| Status |
Public on Jan 17, 2013 |
| Title |
CBFb Stabilizes HIV Vif to Counteract APOBEC3 at the Expense of RUNX1 Target Gene Expression [gene expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
|
| |
|
| Overall design |
Analysis of Vif-dependent effects on gene expression in Jurkats when cells are activated for 4 or 6 hours with PMA and PHA
|
| |
|
| Contributor(s) |
Hartley PD, Krogan NJ |
| Citation(s) |
23333304 |
| |
| Submission date |
Nov 28, 2012 |
| Last update date |
Jan 29, 2013 |
| Contact name |
Nevan Krogan |
| E-mail(s) |
nevan.krogan@ucsf.edu
|
| Phone |
415-476-2980
|
| Fax |
415-514-9736
|
| Organization name |
University of California, San Francisco
|
| Department |
Cellular & Molecular Pharmacology
|
| Lab |
Krogan
|
| Street address |
1700 4th Street
|
| City |
San Francisco |
| ZIP/Postal code |
94158 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16332 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [MMBGX-Ensembl64] |
|
| Samples (12)
|
|
| This SubSeries is part of SuperSeries: |
| GSE42576 |
CBFb Stabilizes HIV Vif to Counteract APOBEC3 at the Expense of RUNX1 Target Gene Expression |
|
| Relations |
| BioProject |
PRJNA182317 |
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