ArticlePLoS pathogens2007
HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase.
Article in PLoS pathogens, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 185 citations in OpenAlex.
- Manipulation of the cell cycle by HIV-1.Biochemical Society transactions · 2026Review
- Structural basis of diverse substrate recruitment by the HIV-1 Vpr-hijacked CRL4(VprBP) E3 ligase.PLoS pathogens · 2026Article
- Article
- HIV-1 Vpr is targeted for degradation by autophagy.PLoS pathogens · 2026Article
- HIV-1 Vif and Vpr cooperatively modulate the cell cycle to maximize per-cell virion production.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HIV-1 Vpr orchestrates ciTRAN upregulation through TGF-β induction.PLoS pathogens · 2025Article
- 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
- Review
- Navigating the Nexus: HIV and Breast Cancer-A Critical Review.International journal of molecular sciences · 2024Review
- HIV-1 Vpr Functions in Primary CD4Viruses · 2024Review
- Caspase cleavage of gasdermin E causes neuronal pyroptosis in HIV-associated neurocognitive disorder.Brain : a journal of neurology · 2024Article
- Article
- E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation.Viruses · 2023Review
- HIV-1 Vpr induces ciTRAN to prevent transcriptional repression of the provirus.Science advances · 2023Article
- Review
- Huntingtin-Interacting Protein 1 Promotes Vpr-Induced G2 Arrest and HIV-1 Infection in Macrophages.Viruses · 2021Article
- Binding to DCAF1 distinguishes TASOR and SAMHD1 degradation by HIV-2 Vpx.PLoS pathogens · 2021Article
- Article
- Human Immunodeficiency Virus Type 1 Vpr Mediates Degradation of APC1, a Scaffolding Component of the Anaphase-Promoting Complex/Cyclosome.Journal of virology · 2021Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) has been shown to cause G2 cell cycle arrest in human cells by inducing ATR-mediated inactivation of p34cdc2, but factors directly engaged in this process remain unknown. We used tandem affinity purification to isolate native Vpr complexes. We found that damaged DNA binding protein 1 (DDB1), viral protein R binding protein (VPRBP), and cullin 4A (CUL4A)--components of a CUL4A E3 ubiquitin ligase complex, DDB1-CUL4A(VPRBP)--were able to associate with Vpr. Depletion of VPRBP by small interfering RNA impaired Vpr-mediated induction of G2 arrest. Importantly, VPRBP knockdown alone did not affect normal cell cycle progression or activation of ATR checkpoints, suggesting that the involvement of VPRBP in G2 arrest was specific to Vpr. Moreover, leucine/isoleucine-rich domain Vpr mutants impaired in their ability to interact with VPRBP and DDB1 also produced strongly attenuated G2 arrest. In contrast, G2 arrest-defective C-terminal Vpr mutants were found to maintain their ability to associate with these proteins, suggesting that the interaction of Vpr with the DDB1-VPRBP complex is necessary but not sufficient to block cell cycle progression. Overall, these results point toward a model in which Vpr could act as a connector between the DDB1-CUL4A(VPRBP) E3 ubiquitin ligase complex and an unknown cellular factor whose proteolysis or modulation of activity through ubiquitination would activate ATR-mediated checkpoint signaling and induce G2 arrest.
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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.