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PMID: 23333304 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

CBFβ stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression.

Molecular cell ·Vol. 49 ·No. 4 ·2013-02-21 ·Pages 632-44

Kim DY, Kwon E, Hartley PD, Crosby DC, Mann S, Krogan NJ, Gross JD

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 CBFβ was shown to form a complex with CRL5-Vif and to be essential for A3 degradation and viral infectivity. We now demonstrate that CBFβ 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-CBFβ holoenzyme forms a well-defined heterohexamer, indicating that Vif simultaneously hijacks CRL5 and CBFβ. Heterodimers of CBFβ and RUNX transcription factors contribute toward the regulation of genes, including those with immune system functions. We show that binding of Vif to CBFβ 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.

MeSH Terms
APOBEC Deaminases Amino Acid Sequence Base Sequence CCAAT-Binding Factor/chemistry,metabolism,physiology Consensus Sequence Core Binding Factor Alpha 2 Subunit/chemistry,metabolism,physiology Cytidine Deaminase Cytosine Deaminase/chemistry,metabolism,physiology Gene Expression Gene Expression Regulation Genes, Reporter HEK293 Cells HIV-1/physiology Host-Pathogen Interactions Humans Hydrophobic and Hydrophilic Interactions Models, Molecular Molecular Sequence Data Protein Binding Protein Interaction Domains and Motifs Protein Multimerization Protein Processing, Post-Translational Protein Stability Protein Structure, Quaternary T-Lymphocytes/metabolism,virology Ubiquitination vif Gene Products, Human Immunodeficiency Virus/chemistry,metabolism,physiology
Chemicals
CCAAT-Binding Factor Core Binding Factor Alpha 2 Subunit RUNX1 protein, human vif Gene Products, Human Immunodeficiency Virus vif protein, Human immunodeficiency virus 1 Cytosine Deaminase APOBEC Deaminases APOBEC3 protein, human Cytidine Deaminase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kim Dong Young
Department of Pharmaceutical Chemistry, University of California, San Francisco (UCSF), San Francisco, CA 94107, USA.
Kwon Eunju
Hartley Paul D
Crosby David C
Mann Sumanjit
Krogan Nevan J
Gross John D
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2012.12.012
Published
2013-02-21
Epub
2013-00-17
Pages
632-44
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3582769
Subset
IM
Grants
NIGMS NIH HHS · P50 GM081879 · United States
NIGMS NIH HHS · P50 GM082250 · United States
NIAID NIH HHS · P30 AI027763 · United States
NCRR NIH HHS · P41 RR001614 · United States
NIAID NIH HHS · P01 AI091575 · United States
NIGMS NIH HHS · R01 GM078360 · United States
NIAID NIH HHS · P01 AI090935 · United States
Databases
GEO
GSE42576
External Links
PubMed source DOI: 10.1016/j.molcel.2012.12.012 PMC Full Text View journal details
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