ArticleThe Journal of biological chemistry2010
HIV-1 Vpr loads uracil DNA glycosylase-2 onto DCAF1, a substrate recognition subunit of a cullin 4A-ring E3 ubiquitin ligase for proteasome-dependent degradation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 102 citations in OpenAlex.
- Structural basis of diverse substrate recruitment by the HIV-1 Vpr-hijacked CRL4(VprBP) E3 ligase.PLoS pathogens · 2026Article
- A real-time FRET ubiquitin transfer assay for quantitative characterization of ternary complexes in targeted protein degradation.Cell reports methods · 2026Article
- OICR-41103 as a chemical probe for the DCAF1 WD40 domain.Communications biology · 2025Article
- Protein-Protein Interactions in Base Excision Repair.Biomolecules · 2025Review
- CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X.Viruses · 2024Review
- HIV-1 Vpr combats the PU.1-driven antiviral response in primary human macrophages.Nature communications · 2024Article
- HIV-1 Vpr Functions in Primary CD4Viruses · 2024Review
- Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4Nature communications · 2024Article
- E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation.Viruses · 2023Review
- Discovery of Nanomolar DCAF1 Small Molecule Ligands.Journal of medicinal chemistry · 2023Article
- Article
- Structure of HIV-1 Vpr in complex with the human nucleotide excision repair protein hHR23A.Nature communications · 2021Article
- The CRL4The EMBO journal · 2021Article
- A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry.Nature communications · 2021Article
- Article
- Vpu modulates DNA repair to suppress innate sensing and hyper-integration of HIV-1.Nature microbiology · 2020Article
- Impact of HIV-1 Vpr manipulation of the DNA repair enzyme UNG2 on B lymphocyte class switch recombination.Journal of translational medicine · 2020Article
- Review
- Deficient uracil base excision repair leads to persistent dUMP in HIV proviruses during infection of monocytes and macrophages.PloS one · 2020Article
- Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The human immunodeficiency virus type 1 (HIV-1) accessory protein, Vpr, interacts with several host cellular proteins including uracil DNA glycosylase-2 (UNG2) and a cullin-RING E3 ubiquitin ligase assembly (CRL4(DCAF1)). The ligase is composed of cullin 4A (CUL4A), RING H2 finger protein (RBX1), DNA damage-binding protein 1 (DDB1), and a substrate recognition subunit, DDB1- and CUL4-associated factor 1 (DCAF1). Here we show that recombinant UNG2 specifically interacts with Vpr, but not with Vpx of simian immunodeficiency virus, forming a heterotrimeric complex with DCAF1 and Vpr in vitro as well as in vivo. Using reconstituted CRL4(DCAF1) and CRL4(DCAF1-Vpr) E3 ubiquitin ligases in vitro reveals that UNG2 ubiquitination (ubiquitylation) is facilitated by Vpr. Co-expression of DCAF1 and Vpr causes down-regulation of UNG2 in a proteasome-dependent manner, with Vpr mutants that are defective in UNG2 or DCAF1 binding abrogating this effect. Taken together, our results show that the CRL4(DCAF1) E3 ubiquitin ligase can be subverted by Vpr to target UNG2 for degradation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.