Affinage

DCAF1

DDB1- and CUL4-associated factor 1 · UniProt Q9Y4B6

Length
1507 aa
Mass
169.0 kDa
Annotated
2026-06-09
100 papers in source corpus 65 papers cited in narrative 64 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DCAF1 (VprBP) is a multifunctional substrate receptor that bridges diverse substrates to cullin-RING ubiquitin ligase machinery, controlling cell cycle progression, genome maintenance, epigenetic silencing, and developmental homeostasis (PMID:18606781, PMID:24028781). Its WD40 domain binds DDB1 stoichiometrically and through DDB1 to CUL4A, assembling the CRL4(DCAF1) E3 complex whose activity is enhanced by LisH-mediated dimerization (PMID:18606781, PMID:21226479); DCAF1 also serves as a substrate receptor for the HECT-type EDD/UBR5 ligase, an unusual dual-service arrangement (PMID:24028781). Through CRL4(DCAF1) it directs polyubiquitylation and proteasomal degradation of an array of substrates including the NF2 tumor suppressor Merlin, the replication factor Mcm10, PP2A scaffold PP2A-A during oocyte meiosis, RAG1 during B-cell V(D)J recombination, p53 (via MDM2), the ribosome assembly factor PWP1, and PLK4 to restrain premature centriole duplication (PMID:18332868, PMID:22570418, PMID:26281983, PMID:22157821, PMID:26728942, PMID:33355139, PMID:38490717). Substrate selection can be encoded by post-translational degrons: a methyl degron generated by EZH2 and read by the DCAF1 chromo domain, or phospho-degrons created by DYRK2 on TERT and AKT on FAM13A (PMID:23063525, PMID:23362280, PMID:23612978, PMID:36749583). Independent of its ligase function, DCAF1 harbors an intrinsic atypical protein kinase activity that phosphorylates histone H2A at threonine 120 to silence tumor-suppressor and anti-osteoclastogenic genes, and phosphorylates non-histone substrates EZH2 (T367) and p53 (S367) to drive epigenetic gene silencing and p53 destabilization (PMID:24140421, PMID:37069142, PMID:37041410, PMID:39587626). DCAF1 governs the Hippo pathway downstream of Merlin by ubiquitylating and inhibiting Lats1/2 to promote YAP/TEAD-dependent oncogenic transcription (PMID:25026211, PMID:24912773). It is essential for proliferation and DNA replication, and its ablation in mice causes early embryonic lethality and selective loss of proliferating cells (PMID:18606781, PMID:33355139). DCAF1 is constitutively hijacked by HIV-1 Vpr and HIV-2/SIV Vpx, which redirect CRL4(DCAF1) to degrade host restriction factors — including SAMHD1, UNG2, HLTF, Exo1, TET2, SIRT7, and TASOR — and to drive Vpr-induced G2 arrest and PLK4-dependent centrosome amplification (PMID:17314515, PMID:17609381, PMID:18606781, PMID:17620334, PMID:20870715, PMID:29883611, PMID:34699574, PMID:38443376). The structural basis for this versatility has been defined by crystal structures of DDB1-DCAF1-Vpr-UNG2 and DCAF1-PROTAC ternary complexes, and DCAF1 has been validated as a covalent E3 handle (via Cys1113) for targeted protein degradation (PMID:27571178, PMID:39580491, PMID:36170674).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 Medium

    Established DCAF1/VprBP as a direct cellular binding partner of HIV-1 Vpr, defining the first molecular handle on its function.

    Evidence In vitro binding, co-IP, and Vpr nuclear-transport assays with VprBP mutational mapping

    PMID:11223251

    Open questions at the time
    • No enzymatic activity assigned
    • Cellular role beyond Vpr sequestration undefined
  2. 2007 High

    Resolved how Vpr exerts its cell-cycle effects by showing DCAF1 is the substrate receptor bridging Vpr to the CUL4-DDB1 E3 ligase, with Vpr binding required for G2 arrest and for boosting ligase activity.

    Evidence Co-IP, AP-MS, neddylation assays, siRNA, and Vpr point mutagenesis with G2-arrest readouts across multiple labs

    PMID:17314515 PMID:17609381 PMID:17620334 PMID:18606781

    Open questions at the time
    • Endogenous (non-Vpr) substrates not yet identified
    • Direct substrate of the G2 arrest unknown
  3. 2008 High

    Defined DCAF1 architecture within CRL4 and its first endogenous substrate, establishing it as a stoichiometric WD40-domain adaptor with cell-cycle-regulated, chromatin-associated, replication-promoting roles essential for viability.

    Evidence Co-IP, chromatin fractionation, BrdU/cell-cycle assays, conditional mouse KO, and Merlin ubiquitination assays

    PMID:18332868 PMID:18606781

    Open questions at the time
    • How chromatin binding directs substrate choice unclear
    • Degron logic for endogenous substrates undefined
  4. 2008 High

    Extended the Vpr paradigm to HIV-2/SIV Vpx, showing Vpx also co-opts DCAF1-CUL4 to enable reverse transcription and infection of macrophages.

    Evidence Proteomic pulldown, co-IP, RNAi, and infection assays measuring reverse transcripts in primary macrophages

    PMID:18464893 PMID:19264781

    Open questions at the time
    • The restriction factor degraded by Vpx not yet identified at this stage
  5. 2010 High

    Linked DCAF1 to tumor suppression by showing nuclear Merlin binds and inhibits CRL4(DCAF1), and reconstituted the Vpr-UNG2 substrate-loading mechanism in vitro.

    Evidence Co-IP, nuclear fractionation, expression profiling, tumorigenicity assays, and in vitro reconstituted UNG2 ubiquitination

    PMID:20178741 PMID:20824083 PMID:20870715

    Open questions at the time
    • Downstream effectors of derepressed CRL4(DCAF1) not yet defined
    • Mechanism of Merlin-mediated inhibition structurally unresolved
  6. 2010 High

    Placed DCAF1 in cell-competition biology by identifying the Drosophila ortholog Mahjong as an Lgl partner acting through JNK-dependent apoptosis.

    Evidence Co-IP and Drosophila/MDCK genetics with JNK pathway manipulation

    PMID:20644714

    Open questions at the time
    • Whether ligase or kinase activity mediates competition unclear at this stage
  7. 2011 High

    Showed CRL4(DCAF1) dimerizes via an N-terminal LisH helix that enhances E3 activity, and identified RAG1 as a CRL4(DCAF1) target required for proper V(D)J recombination.

    Evidence EM, in vitro reconstitution/mutagenesis, and conditional B-cell KO with V(D)J recombination sequencing

    PMID:21226479 PMID:22157821

    Open questions at the time
    • Whether RAG1 is a direct ubiquitylation substrate vs. regulated indirectly unresolved
    • Structural basis of dimer-enhanced catalysis not defined
  8. 2012 Medium

    Revealed degron-based substrate recognition by DCAF1, including chromo-domain reading of EZH2-generated methyl degrons and recruitment of replication factor Mcm10 and constitutive UNG2/SMUG1 turnover.

    Evidence Modeling/binding assays with chromo-domain mutagenesis, in vitro methylation and ubiquitination, and degradation assays

    PMID:22292079 PMID:22570418 PMID:23063525

    Open questions at the time
    • Chromo-domain methyl-reading shown for limited substrates
    • Generality of methyl-degron logic untested
  9. 2013 High

    Discovered that DCAF1 is a moonlighting protein: an intrinsic atypical kinase phosphorylating nucleosomal H2A-T120 to silence tumor-suppressor genes, and a dual-service receptor also serving the HECT-type EDD/UBR5 ligase to degrade TERT and NuRD adaptors.

    Evidence In vitro nucleosomal kinase assays, ChIP, xenografts, EDD-dependent TERT and ZIP degradation, and review synthesis

    PMID:23362280 PMID:23612978 PMID:24028781 PMID:24116224 PMID:24140421

    Open questions at the time
    • Catalytic mechanism of the atypical kinase undefined
    • How kinase vs. ligase activities are coordinated unclear
  10. 2014 High

    Defined the Merlin-DCAF1 interface structurally and the oncogenic output of the pathway, and showed CRL4(DCAF1) monoubiquitylates TET enzymes to control DNA hydroxymethylation in development.

    Evidence Crystal structures of Merlin FERM-DCAF1, Lats1/2 ubiquitination/YAP-TEAD epistasis, and oocyte-specific KO with 5hmC imaging

    PMID:24706749 PMID:24912773 PMID:25026211 PMID:25557551

    Open questions at the time
    • How Merlin inhibition is relieved in tumors not fully resolved
    • Mono- vs. poly-ubiquitylation switching mechanism unclear
  11. 2015 High

    Connected DCAF1 to meiosis and replication-coupled proteolysis through PP2A-A and ESCO2 degradation, and showed Vpr exploits MCM10 as a natural CRL4(DCAF1) substrate.

    Evidence Oocyte-specific KO with genetic rescue, in vitro ubiquitination, cell synchronization, and Vpr-dependent MCM10 degradation assays

    PMID:26032416 PMID:26281983 PMID:30100344

    Open questions at the time
    • Degron features distinguishing replication substrates unclear
    • Coordination with APC/C in ESCO2 turnover not fully defined
  12. 2016 High

    Established DCAF1 as essential for proliferation in part by restraining p53, defined Vpr/Vpx-DCAF1 binding determinants structurally, and mapped the minimal DCAF1-WD module.

    Evidence Conditional T-cell KO with p53-deletion rescue, DDB1-DCAF1-Vpr-UNG2 crystal structure, DICER1 degradation, and DCAF1-WD mutagenesis

    PMID:24558487 PMID:26728942 PMID:26965998 PMID:27571178

    Open questions at the time
    • Direct p53 ubiquitylation by DCAF1 vs. MDM2-mediated effect distinction
    • p53-independent growth function uncharacterized at this stage
  13. 2018 High

    Expanded the Vpr substrate repertoire to HLTF, Exo1, TET2, and CP110, linking DCAF1 hijacking to chromatin remodeling, IL-6-driven viral replication, and centrosomal effects.

    Evidence In vitro reconstitution, mutagenesis, ChIP, conditional KO, and HIV-1 infection assays in T cells

    PMID:29079575 PMID:29724823 PMID:29883611 PMID:30352932

    Open questions at the time
    • Determinants of substrate-loop plasticity not yet structurally defined
    • Physiological roles of CP110 control outside infection unclear
  14. 2020 High

    Broadened DCAF1 biology into redox/aging, antioxidant, and growth-factor signaling through GSTP1/ROS control in Tregs, KEAP1-independent NRF2 degradation, and TGF-beta/Activin receptor turnover, and identified essential ribosome-biogenesis control via PWP1.

    Evidence Conditional KO models, ROS assays, co-IP/ubiquitination, zebrafish embryogenesis, and MS substrate ID with ribosome profiling

    PMID:31291647 PMID:32171724 PMID:32730228 PMID:33355139

    Open questions at the time
    • Whether NRF2 and Rheb degradation use CRL4 or kinase activity not always resolved
    • Tissue-specificity of substrate selection unexplained
  15. 2022 High

    Defined DCAF1 regulation and druggability, showing AR/OGT and USP2 control its abundance to repress p53, and validating Cys1113 as a covalent handle for PROTAC-based targeted degradation.

    Evidence Knockdown, ChIP-seq, USP2 KO/inhibitor tumor models, and chemical proteomics with C1113A mutagenesis and PROTAC assays

    PMID:35348747 PMID:36170674 PMID:37024504

    Open questions at the time
    • Mechanism by which DCAF1 represses p53 in prostate cancer (kinase vs. ligase) not fully resolved
  16. 2023 High

    Consolidated the atypical-kinase axis by showing DCAF1 phosphorylates EZH2-T367 to elevate H3K27me3 and p53-S367 to promote its degradation, defining a kinase-driven epigenetic silencing and tumor-suppressor-restraint program.

    Evidence In vitro kinase assays, phospho-specific antibodies, T367A/S367A mutagenesis, ChIP, organoid and xenograft models, and FAM13A phospho-degron mapping

    PMID:36749583 PMID:37041410 PMID:37069142

    Open questions at the time
    • Substrate-selection rules of the atypical kinase undefined
    • Structural basis of the kinase domain unresolved
  17. 2024 High

    Resolved the dual, opposing relationship between DCAF1 and PLK4/centriole control and the structural plasticity enabling diverse substrate recruitment, while extending DCAF1 to glucose sensing, innate immunity, and HIV latency.

    Evidence AP-MS, reciprocal co-IP, PLK4 mutant/ubiquitination assays, DCAF1-PROTAC-WDR5 crystal structures, and metabolic, IFN, and LTR/NF-kB functional assays

    PMID:38443376 PMID:38490717 PMID:38862475 PMID:38905100 PMID:39580491 PMID:39587626 PMID:40370558

    Open questions at the time
    • How Vpr converts DCAF1-PLK4 from degradation to procentriole recruitment mechanistically unclear
    • Integration of metabolic vs. immune substrate programs undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DCAF1 partitions between its CRL4 ligase, EDD/UBR5 ligase, and intrinsic kinase activities — and what governs context-dependent substrate selection across its very broad target list — remains unresolved.
  • No structure of the DCAF1 kinase domain or its substrate-recognition mode
  • No unifying model for switching between ligase and kinase functions
  • Determinants directing tissue- and signal-specific substrate choice unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0060090 molecular adaptor activity 5 GO:0016740 transferase activity 4 GO:0042393 histone binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005815 microtubule organizing center 3 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3
Partners
CUL4ADDB1DYRK2EZH2NF2PLK4TP53UNG2
Complex memberships
CRL4(DCAF1) (DDB1-CUL4A-ROC1-DCAF1)EDD-DYRK2-DDB1(DCAF1) complexEDD/UBR5 E3 ligase complex

Evidence

Reading pass · 64 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 DCAF1/VprBP (KIAA0800) was cloned as a 1507-aa cytoplasmic protein that directly binds HIV-1 Vpr in vitro and in vivo; the Vpr-binding domain was mapped to the C-terminal half of VprBP containing a Pro-rich domain and Phe-x-x-Phe repeats. Co-expression of VprBP sequesters Vpr in the cytoplasm, blocking its nuclear transport. In vitro binding assay with recombinant proteins, co-immunoprecipitation, subcellular fractionation, adenoviral expression, Vpr-GFP nuclear transport assay, VprBP mutational analysis Gene Medium 11223251
2007 DCAF1/VprBP serves as the substrate receptor bridging HIV-1 Vpr to the Cul4-DDB1 ubiquitin ligase complex; this interaction is essential for Vpr-induced G2 cell cycle arrest, which is abolished by single Vpr mutations impairing DCAF1 binding or by siRNA-mediated DCAF1 silencing. Co-immunoprecipitation, siRNA knockdown, cell cycle analysis (G2 arrest assay), point mutagenesis of Vpr Cell cycle (Georgetown, Tex.) High 17314515 17609381 18606781
2007 Vpr binding to the VprBP subunit of the Cul4-DDB1[VprBP] E3 complex increases neddylation and intrinsic ubiquitin ligase activity of this E3. VprBP also has an independent role in regulating G1 phase and is required for completion of DNA replication in S phase. Affinity purification/mass spectrometry, co-immunoprecipitation, neddylation assay, siRNA knockdown with cell cycle analysis Proceedings of the National Academy of Sciences of the United States of America Medium 17609381
2007 HIV-1 Vpr engages the DDB1- and CUL4A-containing ubiquitin ligase complex through VprBP/DCAF1; both the Vpr–VprBP interaction and assembly of the full ubiquitin ligase are necessary for Vpr-mediated G2 arrest. Co-immunoprecipitation, tandem mass spectrometry, functional G2 arrest assay The Journal of biological chemistry High 17620334
2008 DCAF1/VprBP functions as the substrate adaptor that recruits Merlin (NF2) to the Roc1-Cul4A-DDB1 E3 ligase complex for polyubiquitination and proteasome-mediated degradation following serum stimulation; VprBP depletion stabilizes Merlin and inhibits ERK and Rac1 activation. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, western blot for ERK/Rac activation Oncogene Medium 18332868
2008 VprBP/DCAF1 binds stoichiometrically with DDB1 through its WD40 domain and through DDB1 to CUL4A; steady-state VprBP decreases during mitosis, and VprBP binds chromatin in a DDB1-independent, cell cycle-dependent manner (peaks in G2). Silencing VprBP reduces DNA replication rate, blocks S-phase progression, and VprBP ablation in mice causes early embryonic lethality. Co-immunoprecipitation, chromatin fractionation, cell cycle synchronization, siRNA knockdown, BrdU incorporation, conditional mouse knockout Molecular and cellular biology High 18606781
2008 HIV-2/SIVmac Vpx associates with VprBP/DCAF1 and the Cullin 4 E3 complex; this interaction is required for efficient reverse transcription of SIVmac in primary macrophages. Depletion of VprBP by RNAi renders macrophages resistant to SIVmac infection. Biochemical and proteomic pulldown, co-immunoprecipitation, siRNA knockdown, infection assay measuring reverse transcripts PLoS pathogens High 18464893 19264781
2009 HIV-2 Vpx assembles with CUL4A-DDB1 through DCAF1 recruitment; preventing Vpx from recruiting DCAF1 in target macrophages causes a post-entry block with defective accumulation of reverse transcripts, and SIVsm Vpx functionally complements Vpx-defective HIV-2 in a DCAF1-binding-dependent manner. Co-immunoprecipitation, siRNA knockdown, viral infection assay, reverse transcription quantification Journal of virology High 19264781
2010 Merlin (NF2 tumor suppressor) in its closed growth-inhibitory form translocates to the nucleus, directly binds CRL4(DCAF1), and suppresses its E3 ubiquitin ligase activity. DCAF1 depletion blocks the pro-mitogenic effect of Merlin inactivation; tumor-derived mutations disrupt Merlin–DCAF1 interaction. Co-immunoprecipitation, siRNA knockdown, nuclear fractionation, gene expression profiling, schwannoma cell proliferation assays, tumor cell line tumorigenicity assays Cell High 20178741
2010 HIV-1 Vpr loads UNG2 onto DCAF1 forming a heterotrimeric VprBP–Vpr–UNG2 complex in vitro and in vivo; reconstituted CRL4(DCAF1-Vpr) E3 ubiquitin ligase ubiquitinates UNG2 in vitro, and co-expression of DCAF1 with Vpr causes proteasome-dependent UNG2 degradation. In vitro reconstitution with recombinant proteins, in vitro ubiquitination assay, co-immunoprecipitation, proteasome inhibitor rescue The Journal of biological chemistry High 20870715
2010 Vpr forms mobile chromatin-associated nuclear foci containing VPRBP/DCAF1; Vpr associates with chromatin via its C-terminal domain and forms a complex with VPRBP on chromatin. These nuclear foci are required for G2 arrest; VPRBP depletion does not prevent foci formation but does prevent G2 arrest. Immunofluorescence, confocal microscopy, time-lapse microscopy, chromatin fractionation, co-immunoprecipitation, siRNA knockdown PLoS pathogens Medium 20824083
2010 Mahjong/VprBP (Drosophila ortholog of DCAF1) is a novel binding partner of Lgl (lethal giant larvae) in both flies and mammals; mahj mutant cells undergo apoptosis when surrounded by wild-type cells via the JNK pathway, establishing that Mahjong and Lgl function in the same pathway to regulate cellular competitiveness. Biochemical immunoprecipitation, Drosophila genetics (wing disc analysis), RNAi knockdown in MDCK cells, JNK pathway inhibition PLoS biology High 20644714
2011 CRL4-DCAF1 complex dimerizes via a short helical region (residues 845–873, designated LisH motif) N-terminal to DCAF1's WD40 domain; four Leu residues in this helix are essential for oligomerization. Dimeric CRL4(DCAF1) is more active as an E3 ligase for UNG2 ubiquitination in vitro than monomeric complex. Electron microscopy, in vitro reconstitution, in vitro ubiquitination assay, mutagenesis of oligomerization helix Biochemistry High 21226479
2011 VprBP/DCAF1 associates with full-length RAG1 through a multi-subunit CRL4 complex (VprBP/DDB1/Cul4A/Roc1); conditional B-lineage VprBP disruption arrests B-cell development at the pro-B to pre-B transition with severely impaired V(D)J recombination and increased error-prone repair. Co-immunoprecipitation, in vitro ubiquitylation, conditional B-cell specific knockout mouse, flow cytometry, V(D)J recombination assay, sequencing of coding joints The EMBO journal High 22157821
2012 DCAF1's putative chromo domain directly recognizes monomethylated substrates generated by EZH2; mutations in the DCAF1 chromo domain binding pocket abolish binding to monomethylated substrates. EZH2 methylates RORα, creating a methyl degron recognized by DCAF1/DDB1/CUL4 for ubiquitin-mediated degradation. Molecular modeling, binding affinity assays, mutagenesis of DCAF1 chromo domain, in vitro methylation assay, ubiquitination assay Molecular cell Medium 23063525
2012 A conserved Wx4Φx2Φx3AΦxH motif in SIVmac Vpx and HIV-1 Vpr is required for DCAF1 interaction and Vpx-mediated SAMHD1 degradation. DCAF1 and SAMHD1 interactions in Vpx involve distinct interfaces; VpxW24A mutants still bind DCAF1 and SAMHD1 but cannot trigger SAMHD1 degradation. Mutational analysis, co-immunoprecipitation, SAMHD1 degradation assay, viral infection assay Cellular microbiology Medium 22776683
2012 CRL4-DDB1-VprBP/DCAF1 ubiquitin ligase mediates stress-induced (UV) proteolysis of the DNA replication factor Mcm10; VprBP is the substrate recognition subunit that targets Mcm10. The purified Cul4-Roc1-DDB1 complex ubiquitinates Mcm10 in vitro. Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown, UV irradiation assay Nucleic acids research High 22570418
2012 DCAF1/VprBP constitutively targets UNG2 and SMUG1 for CRL4(DCAF1)-mediated degradation independently of Vpr; UNG2 assembles with the ubiquitin ligase complex in the absence of Vpr, but Vpr enhances this interaction at low Vpr concentrations while high Vpr concentrations block UNG2 depletion. Co-immunoprecipitation, siRNA knockdown, proteasome inhibitor rescue, cell fractionation PloS one Medium 22292079
2013 VprBP/DCAF1 possesses intrinsic protein kinase activity and phosphorylates histone H2A on threonine 120 (H2AT120) in a nucleosomal context; VprBP localizes to tumor suppressor gene loci and blocks their transcription in a kinase-activity-dependent manner. In vitro kinase assay with nucleosomes, mutagenesis of kinase domain, ChIP, RNAi knockdown, small-molecule inhibitor studies, xenograft tumor growth Molecular cell High 24140421
2013 Dyrk2 phosphorylates TERT, creating a phospho-degron recognized by the EDD-DDB1-VprBP/DCAF1 E3 ligase complex, leading to TERT ubiquitination and degradation; this regulation is cell cycle-dependent (G2/M phase) and telomerase activity is constitutively elevated upon Dyrk2 depletion. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, siRNA knockdown, telomerase activity assay, cell cycle synchronization The Journal of biological chemistry High 23362280 23612978
2013 VprBP/DCAF1 serves as a substrate recognition subunit for both the RING-type CRL4 ligase and the HECT-type EDD/UBR5 ligase, representing an unusual dual-service substrate receptor. Review synthesizing biochemical and proteomic data from primary studies (co-immunoprecipitation, mass spectrometry) BMC molecular biology Medium 24028781
2013 HIV-1 Vpr induces degradation of ZIP and sZIP (NuRD complex adaptors) by hijacking DCAF1; ZIP/sZIP degradation requires proteasome activity and is abolished by a DCAF1-binding-deficient Vpr mutant or DCAF1 siRNA knockdown. Vpr co-localizes with Cul4A ligase subunits exclusively on chromatin. Co-immunoprecipitation, siRNA knockdown, proteasome inhibitor rescue, cellular fractionation PloS one Medium 24116224
2014 Derepressed CRL4(DCAF1) promotes YAP/TEAD-dependent transcription by ubiquitylating and inhibiting Lats1 and Lats2 in the nucleus; genetic epistasis experiments confirm this signaling axis sustains oncogenicity of Merlin-deficient tumor cells. Co-immunoprecipitation, ubiquitination assay, genetic epistasis (double knockdown/overexpression), YAP/TEAD reporter assay, analysis of NF2-mutant tumor samples Cancer cell High 25026211
2014 CRL4(VprBP/DCAF1) monoubiquitylates all three TET dioxygenases on a conserved lysine (K1299 for TET2), promoting TET chromatin binding; deletion of VprBP in oocytes abrogates paternal DNA hydroxymethylation in zygotes. Leukemia-derived TET2 inactivating mutations target either the monoubiquitylation site or VprBP-binding residues. Co-immunoprecipitation, in vitro ubiquitination assay, conditional oocyte-specific VprBP knockout mouse, 5hmC immunofluorescence, mutational analysis Molecular cell High 25557551
2014 Crystal structure of the Merlin FERM domain bound to the DCAF1 C-terminal acidic tail reveals that the hydrophobic IILXLN motif of DCAF1 binds subdomain C of the FERM domain as a β-strand; CD44 cytoplasmic tail competes with DCAF1 for binding to the same Merlin FERM binding groove. X-ray crystallography, competition binding assay Genes to cells : devoted to molecular & cellular mechanisms High 24912773
2014 Crystal structure of the Merlin FERM domain in complex with DCAF1 binding domain reveals that the Merlin-FERM binding domain of DCAF1 folds as a β-hairpin and binds the α1/β5-groove of the F3 lobe via extensive hydrophobic interactions. X-ray crystallography The Journal of biological chemistry High 24706749
2014 The minimal DCAF1-WD domain (residues 1041–1393) retains Vpr and DDB1 binding; an α-helical H-box motif and F/YxxF/Y motifs in the N-terminal portion of DCAF1-WD are required exclusively for DDB1 binding; Vpr binding to DCAF1 modulates DDB1/DCAF1 complex formation, and expression of DCAF1-WD alone is insufficient for Vpr-mediated G2 arrest. Mutagenesis, co-immunoprecipitation, G2 arrest functional assay PloS one Medium 24558487
2015 CRL4-DCAF1 controls oocyte meiotic maturation by directing proteasomal degradation of PP2A scaffold subunit PP2A-A; oocyte-specific deletion of DDB1 or DCAF1 causes PP2A-A accumulation and meiosis failure; combined deletion of Ppp2r1a rescues meiotic defects. Oocyte-specific conditional knockout mouse, in vitro ubiquitination assay (DCAF1 directly ubiquitinates PP2A-A), genetic rescue (double KO), western blot Nature communications High 26281983
2015 HIV-1 Vpr indirectly binds MCM10 (DNA replication factor) in a VprBP-dependent manner; Vpr enhances ubiquitination and proteasomal degradation of MCM10, and this correlates with Vpr-induced G2/M arrest. MCM10 is identified as a natural substrate of Cul4-DDB1[VprBP]. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor rescue, G2/M arrest analysis The Journal of biological chemistry Medium 26032416
2015 Lgl associates with the VprBP-DDB1 complex independently of the PAR-aPKC complex and prevents VprBP-DDB1 from binding CUL4A, thereby inhibiting CRL4[VprBP] E3 ligase activity. aPKC-mediated phosphorylation of Lgl2 negatively regulates Lgl2–VprBP-DDB1 interaction; depletion of VprBP or Cul4 rescues overproliferation of Lgl-depleted cells. Co-immunoprecipitation, siRNA knockdown, cell proliferation assay, phosphomimetic mutant analysis Molecular biology of the cell Medium 25947136
2016 Crystal structure of the DDB1-DCAF1-HIV-1 Vpr-UNG2 complex reveals how Vpr engages DCAF1 and creates a new binding surface for UNG2 recruitment via molecular mimicry of DNA by a Vpr variable loop; Vpr and Vpx use similar N-terminal/helical regions to bind DCAF1 but different regions to recruit their specific substrates. X-ray crystallography Nature structural & molecular biology High 27571178
2016 DCAF1 is essential for T-cell growth, cell cycle entry, and proliferation upon activation; DCAF1 deletion stabilizes p53 protein by impairing MDM2-mediated p53 poly-ubiquitination, and p53 deletion rescues the cell cycle defect but not the growth defect of DCAF1-deficient T cells. Conditional T-cell-specific DCAF1 knockout mouse, flow cytometry, western blot, genetic rescue (p53 deletion), ubiquitination assay Nature communications High 26728942
2016 CUL4A(DCAF1) E3 ubiquitin ligase targets DICER1 for proteasomal degradation in response to Jak-STAT3 pathway activation; PI3K-AKT-mediated phosphorylation of DICER1 contributes to its degradation by this complex. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, xenograft tumor model Cancer letters Medium 26965998
2017 VprBP/DCAF1 promotes FoxM1 ubiquitylation and degradation via CRL4; paradoxically, VprBP also activates FoxM1 transcription through a ligase-independent mechanism. VprBP binding to CRL4 is reduced during mitosis, and VprBP activation of FoxM1 is independent of ubiquitin ligase function. Co-immunoprecipitation, ubiquitination assay, FoxM1 transcriptional reporter assay, cell synchronization, siRNA knockdown Molecular and cellular biology Medium 28416635
2017 Zinc coordination via a conserved zinc-binding motif in Vpx and Vpr is required for CRL4(DCAF1) E3 ligase assembly and DCAF1 interaction; zinc chelation by TPEN selectively inhibits Vpx/Vpr–DCAF1 binding and blocks SAMHD1/HLTF degradation and viral infection, without affecting Vpx–SAMHD1 interaction. Co-immunoprecipitation, mutagenesis of zinc-binding motif, zinc chelation (TPEN treatment), SAMHD1/HLTF degradation assays, viral infection assay Journal of virology Medium 28202763
2017 HIV-1 Vpr directly loads HLTF onto the C-terminal WD40 domain of DCAF1 in the CRL4 complex for polyubiquitination; Vpr interacts with DNA-binding residues in the HIRAN domain of HLTF (similar to UNG2 recruitment) and additionally engages a second region connecting the HIRAN and ATPase/helicase domains. In vitro reconstitution ubiquitination assay, mutational analysis, co-immunoprecipitation The Journal of biological chemistry High 29079575
2018 HIV-1 Vpr targets TET2 for polyubiquitylation by the VprBP-DDB1-CUL4-ROC1 E3 ligase and subsequent proteasomal degradation; Vpr-mediated TET2 degradation sustains IL-6 expression by reducing HDAC1/2 recruitment to the IL-6 promoter, enhancing H3K27 acetylation, thereby promoting HIV-1 replication. Co-immunoprecipitation, in vitro ubiquitination assay, conditional TET2 knockout, chromatin immunoprecipitation, IL-6 ELISA, viral replication assay Molecular cell High 29883611
2018 HIV-1 Vpr recruits Exo1 (exonuclease 1) to the CRL4DCAF1 E3 complex for ubiquitination and proteasomal degradation; Exo1 inhibits HIV-1 replication in T cells, and antagonism of Exo1 is conserved across main group HIV-1 and SIVcpz Vpr proteins. Focused substrate screen, co-immunoprecipitation, ubiquitination assay, HIV replication assay with Exo1 knockdown/overexpression, evolutionary conservation analysis mBio Medium 30352932
2018 CUL4-DDB1-VPRBP E3 ubiquitin ligase complex promotes post-replicative ESCO2 degradation in late S phase; ESCO2 physically interacts with the complex and its degradation requires both CUL4-DDB1-VPRBP and the anaphase-promoting complex. Co-immunoprecipitation, cell synchronization, proteasome inhibitor rescue, siRNA knockdown Current biology : CB Medium 30100344
2018 Vpr localizes to the centrosome through DCAF1, forming a complex with EDD-DYRK2-DDB1(DCAF1) and Cep78; Vpr enhances ubiquitination of CP110 (an EDD substrate) leading to its degradation, causing centriole elongation and increased microtubule nucleation. Infection with HIV-1 (but not Vpr-deleted HIV-1) promotes CP110 degradation in T lymphocytes. Co-immunoprecipitation, immunofluorescence/confocal microscopy, ubiquitination assay, HIV-1 infection assay The Journal of biological chemistry Medium 29724823
2020 DCAF1 is downregulated in aged Tregs and restrains Treg aging via reactive oxygen species regulated by GSTP1 (glutathione-S-transferase P); the DCAF1/GSTP1/ROS axis controls Treg senescence, proliferation, and suppressive function. Conditional T-cell-specific DCAF1 knockout mouse, ROS assays, inflammatory bowel disease model, irradiation-induced aging model, GSTP1 inhibition experiments The Journal of clinical investigation High 32730228
2020 DCAF1 targets NRF2 for proteasomal degradation in a KEAP1-independent manner; DCAF1 directly interacts with NRF2, and small molecule BC-1901S disrupts NRF2/DCAF1 interaction to stabilize NRF2. High-throughput screening, co-immunoprecipitation, ubiquitination assay, NRF2 stability assay, anti-oxidant gene expression Redox biology Medium 32171724
2020 DCAF1 loss in multiple tissues selectively eliminates proliferating cells and causes perinatal lethality, thymic atrophy, and bone marrow defects; DCAF1 targets ribosome assembly factor PWP1 for degradation — DCAF1 loss causes PWP1 accumulation that impairs rRNA processing and ribosome biogenesis, leading to free RPL11 increase and L11-MDM2 association with p53 activation. Conditional tissue-specific knockout mice (multiple tissues), inducible KO in T cells and MEFs, mass spectrometry substrate identification, ribosome profiling, ubiquitination assay, siRNA/overexpression rescue experiments Science advances High 33355139
2021 HIV-1 Vpr mediates poly-ubiquitination and degradation of SIRT7 (histone H3 deacetylase) via CRL4-DCAF1; in vitro reconstitution assays confirm Vpr-induced SIRT7 polyubiquitination. SIRT7 degradation by Vpr is conserved across multiple HIV-1 strains (not HIV-2) and is independent of the Vpr-induced G2 arrest phenotype. In vitro reconstitution ubiquitination assay, co-immunoprecipitation, proteasome inhibitor rescue, Vpr mutant analysis Virology journal High 33648539
2021 HIV-2 Vpx bridges SAMHD1 to DCAF1 for degradation, while TASOR (HUSH complex component) interacts with DCAF1 independently of Vpx; Vpx stabilizes the TASOR–DCAF1 association. TASOR degradation requires a robust Vpx–DCAF1 interaction mediated by TASOR's N-terminal PARP-like domain. Co-immunoprecipitation, Vpx mutagenesis, TASOR/SAMHD1 degradation assays in macrophages PLoS pathogens Medium 34699574
2022 Electrophilic azetidine acrylamides stereoselectively and site-specifically react with Cys1113 (C1113) in DCAF1; this covalent modification supports PROTAC-mediated targeted protein degradation in human cells. A C1113A DCAF1 mutant abolishes PROTAC activity, and only low fractional DCAF1 engagement is required for degradation. Chemical proteomics (activity-based protein profiling), DCAF1 C1113A mutagenesis, PROTAC cell-based degradation assay, stereochemical profiling Journal of the American Chemical Society High 36170674
2022 DCAF1 is regulated by the androgen receptor (AR) at the transcript level and stabilized by OGT at the protein level; DCAF1 knockdown in prostate cancer cells increases p53 stabilization and nucleolar fragmentation, restraining p53 activation downstream of AR and OGT. siRNA knockdown, western blot, flow cytometry, ChIP-seq, clinical sample correlation Molecular cancer research : MCR Medium 35348747
2022 Mahjong/DCAF1 loss in Drosophila cells triggers Xrp1 bZip transcription factor expression, which activates JNK signaling, autophagosome accumulation, eIF2α phosphorylation, and reduced translation — this pathway is independent of apical-basal polarity and couples DCAF1 to protein turnover/cell competition. Drosophila genetics (mahj, ddb1, cul4 mutants), epistasis analysis with xrp1, JNK pathway reporters, translation assays Development (Cambridge, England) Medium 36278853
2023 VprBP/DCAF1 kinase phosphorylates EZH2 at T367, augmenting its nuclear stabilization and methyltransferase activity; DCAF1-mediated EZH2 T367 phosphorylation elevates H3K27me3 levels and silences growth-regulatory genes in colon cancer cells. EZH2 requires this phosphorylation for its oncogenic function in organoid and xenograft models. In vitro kinase assay, phospho-specific antibody, mutagenesis (T367A), ChIP, organoid model, xenograft model Nature communications High 37069142
2023 VprBP/DCAF1 phosphorylates p53 at serine 367 (S367) through a direct interaction with p53's C-terminal domain; S367 phosphorylation promotes p53 proteasomal degradation and suppresses p53 transcriptional activity. p53 acetylation abrogates VprBP–p53 interaction and prevents S367 phosphorylation during DNA damage response. In vitro kinase assay, phospho-specific antibody, p53 S367A/S367E mutagenesis, co-immunoprecipitation, western blot stability assay Oncogene High 37041410
2023 USP2 deubiquitinase stabilizes VPRBP/DCAF1 protein; VPRBP is a potent p53 repressor whose stability is controlled by USP2. VPRBP also regulates PD-L1 expression, and USP2 inhibition combined with anti-PD1 leads to complete tumor regression in wild-type p53 tumors. Co-immunoprecipitation, ubiquitination assay, USP2 inhibitor treatment, Usp2 knockout mouse, tumor regression assay Nature communications Medium 37024504
2023 AKT phosphorylates FAM13A at serine 312, which is then recognized by the CUL4A/DCAF1 E3 ligase complex, leading to FAM13A ubiquitination and proteasomal degradation. Co-immunoprecipitation, ubiquitination assay, phosphomimetic/phosphodeficient mutagenesis, in vivo lung injury models American journal of respiratory cell and molecular biology Medium 36749583
2024 Vpr forms a cooperative ternary complex with VprBP/DCAF1 and PLK4 (polo-like kinase 4); this complex promotes PLK4 relocalization to the procentriole assembly and induces centrosome amplification and aneuploidy in CD4+ T cells. The VprBP acidic region and Vpr C-terminal 17 residues are both required for PLK4 binding. Affinity purification, co-immunoprecipitation, biochemical reconstitution, confocal microscopy, Vpr deletion mutagenesis, primary CD4+ T cell infection assay Nature communications High 38443376
2024 CRL4DCAF1 E3 ubiquitin ligase targets PLK4 for ubiquitylation and degradation in G2 phase to prevent premature centriole duplication; DCAF1 interaction with PLK4 is mediated by PLK4 polo-boxes 1 and 2 and is independent of PLK4 kinase activity, distinguishing it from SCFβ-TrCP-mediated PLK4 regulation. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, PLK4 mutant analysis, cell cycle analysis Life science alliance Medium 38490717
2024 Glucose deprivation transactivates DCAF1 expression, which then promotes K48-linked polyubiquitination and proteasomal degradation of Rheb, inhibiting mTORC1 activity and inducing autophagy to promote cancer cell survival; DCAF1 is identified as a cellular glucose sensor. Co-immunoprecipitation, ubiquitination assay (K48-linkage specific), DCAF1 knockdown/overexpression, mTORC1 activity assay, autophagy assay Cell death & disease Medium 38862475
2024 DOT1L-mediated H3K79me2 recruits DCAF1 to the HIV-1 LTR; upon TNF-α/NF-κB activation, DCAF1 at the LTR ubiquitinates NF-κB and restricts its accumulation at the viral promoter, constituting a feedback repression of HIV reactivation. Peptide affinity purification, proteomics, co-immunoprecipitation, ChIP, siRNA knockdown, HIV-1 reactivation assay Cell reports Medium 38905100
2024 STK39 kinase interacts with PPP2R1A (PP2A scaffold subunit) in a kinase-activity-dependent manner and inhibits DCAF1-mediated PPP2R1A degradation, thereby stabilizing PP2A, which suppresses IRF3 phosphorylation and type I interferon production to promote viral immune escape. Mass spectrometry, co-immunoprecipitation, siRNA knockdown, interferon reporter assay, PP2A phosphatase activity assay, in vivo viral infection model Acta pharmaceutica Sinica. B Medium 40370558
2024 Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes at high resolution reveal that DCAF1 loops provide surface plasticity for substrate recruitment, enabling DCAF1 to accommodate diverse substrates as an E3 ligase substrate receptor. X-ray crystallography of ternary complexes, PROTAC-mediated WDR5 degradation assay in cells Nature communications High 39580491
2024 VprBP/DCAF1 stimulates RANKL-induced osteoclast differentiation by phosphorylating H2AT120 to suppress anti-osteoclastogenic genes; abrogating VprBP kinase activity toward H2AT120 blocks osteoclast differentiation in vitro and in vivo. In vitro kinase assay, VprBP kinase-dead mutant, RANKL-induced osteoclast differentiation assay, in vivo bone loss model, ChIP Epigenetics & chromatin Medium 39587626
2020 VprBP negatively regulates TGF-β and Activin signaling by promoting Smad7-Smurf1-TβRI complex formation, inducing proteasomal degradation of TGF-β type I receptor (TβRI), and stabilizing Smurf1 by suppressing its poly-ubiquitination; VprBP was identified as a novel Smad7 binding partner. Proteomic interaction screen, co-immunoprecipitation, ubiquitination assay, TGF-β signaling (Smad2 phosphorylation, Smad2-Smad4 interaction), zebrafish embryogenesis assay Journal of molecular cell biology Medium 31291647
2013 Autophagy selectively targets VPRBP/DCAF1 for degradation via the LC3B-p62 receptor pathway; VPRBP is a novel LC3B-binding protein, and induction of autophagy reduces VPRBP levels in a manner rescuable by autophagy inhibitors. GST-LC3B pulldown combined with LC-MS/MS, co-immunoprecipitation (VPRBP-LC3/p62 complex), autophagy induction/inhibition with BFA1 and ATG5 knockdown Clinical science (London, England : 1979) Medium 22963397
2019 The carboxyl-terminal ED-rich region (1312–1417) of DCAF1 is required for nuclear localization of DCAF1 and for Vpx-DCAF1 interaction; Merlin and Vpx bind separate regions of DCAF1 (Merlin is resistant to displacement by Vpx). The DCAF1(1-1311) truncation mutant acts as a dominant negative inhibiting Vpx-mediated SAMHD1 degradation. DCAF1 truncation/mutagenesis, co-immunoprecipitation, SAMHD1 degradation assay, nuclear localization imaging Biochemical and biophysical research communications Medium 31003777
2018 VprBP/DCAF1 regulates RAG1 expression post-transcriptionally and independently of Dicer; loss of VprBP stabilizes RAG1 protein via a mechanism requiring both 20S proteasome and CRL4 ubiquitin ligase activity, and RAG1 stabilization by cullin-RING E3 inhibition promotes V(D)J recombination in pre-B cells. Conditional B-cell VprBP KO mouse, western blot (RAG1 stability), cullin-RING inhibitor (MLN4924), pre-B cell V(D)J recombination assay Journal of immunology (Baltimore, Md. : 1950) Medium 29925675
2025 DCAF1 interacts with PARD3 (Par3 polarity protein) and enhances PARD3 expression to activate the Akt signaling pathway, promoting hepatocellular carcinoma growth and metastasis. Co-immunoprecipitation, mass spectrometry, siRNA knockdown and overexpression, RNA sequencing, in vivo xenograft Journal of experimental & clinical cancer research : CR Low 38711082

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell 273 20178741
2007 HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase. Cell cycle (Georgetown, Tex.) 227 17314515
2012 EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Molecular cell 208 23063525
2014 Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-mediated inhibition of the hippo pathway kinases Lats1 and 2 in the nucleus. Cancer cell 205 25026211
2007 Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proceedings of the National Academy of Sciences of the United States of America 204 17609381
2008 Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection. PLoS pathogens 187 18464893
2010 Involvement of Lgl and Mahjong/VprBP in cell competition. PLoS biology 147 20644714
2007 The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptor. The Journal of biological chemistry 137 17620334
2020 DCAF1 regulates Treg senescence via the ROS axis during immunological aging. The Journal of clinical investigation 133 32730228
2009 The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection. Journal of virology 110 19264781
2022 Targeted Protein Degradation by Electrophilic PROTACs that Stereoselectively and Site-Specifically Engage DCAF1. Journal of the American Chemical Society 102 36170674
2010 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. The Journal of biological chemistry 91 20870715
2001 Cytoplasmic retention of HIV-1 regulatory protein Vpr by protein-protein interaction with a novel human cytoplasmic protein VprBP. Gene 90 11223251
2014 CRL4(VprBP) E3 ligase promotes monoubiquitylation and chromatin binding of TET dioxygenases. Molecular cell 89 25557551
2018 Vpr Targets TET2 for Degradation by CRL4VprBP E3 Ligase to Sustain IL-6 Expression and Enhance HIV-1 Replication. Molecular cell 83 29883611
2016 The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction. Nature structural & molecular biology 82 27571178
2008 Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Molecular and cellular biology 78 18606781
2024 DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance. Nature communications 71 38177131
2015 CRL4-DCAF1 ubiquitin E3 ligase directs protein phosphatase 2A degradation to control oocyte meiotic maturation. Nature communications 68 26281983
2013 Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation. The Journal of biological chemistry 61 23362280
2008 VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. Oncogene 58 18332868
2012 Lentivirus Vpr and Vpx accessory proteins usurp the cullin4-DDB1 (DCAF1) E3 ubiquitin ligase. Current opinion in virology 56 23062609
2010 Formation of mobile chromatin-associated nuclear foci containing HIV-1 Vpr and VPRBP is critical for the induction of G2 cell cycle arrest. PLoS pathogens 55 20824083
2012 A novel DCAF1-binding motif required for Vpx-mediated degradation of nuclear SAMHD1 and Vpr-induced G2 arrest. Cellular microbiology 52 22776683
2015 HIV-1 Vpr Protein Enhances Proteasomal Degradation of MCM10 DNA Replication Factor through the Cul4-DDB1[VprBP] E3 Ubiquitin Ligase to Induce G2/M Cell Cycle Arrest. The Journal of biological chemistry 48 26032416
2013 VprBP has intrinsic kinase activity targeting histone H2A and represses gene transcription. Molecular cell 48 24140421
2023 Discovery of Nanomolar DCAF1 Small Molecule Ligands. Journal of medicinal chemistry 42 36948210
2020 CRL4DCAF1/VprBP E3 ubiquitin ligase controls ribosome biogenesis, cell proliferation, and development. Science advances 42 33355139
2013 HIV-1 Vpr protein inhibits telomerase activity via the EDD-DDB1-VPRBP E3 ligase complex. The Journal of biological chemistry 42 23612978
2016 Jak-STAT3 pathway triggers DICER1 for proteasomal degradation by ubiquitin ligase complex of CUL4A(DCAF1) to promote colon cancer development. Cancer letters 41 26965998
2012 CRL4-DDB1-VPRBP ubiquitin ligase mediates the stress triggered proteolysis of Mcm10. Nucleic acids research 41 22570418
2017 VprBP/DCAF1 Regulates the Degradation and Nonproteolytic Activation of the Cell Cycle Transcription Factor FoxM1. Molecular and cellular biology 40 28416635
2013 VprBP (DCAF1): a promiscuous substrate recognition subunit that incorporates into both RING-family CRL4 and HECT-family EDD/UBR5 E3 ubiquitin ligases. BMC molecular biology 40 24028781
2014 miRNA-1236 inhibits HIV-1 infection of monocytes by repressing translation of cellular factor VprBP. PloS one 38 24932481
2012 The HIV1 protein Vpr acts to enhance constitutive DCAF1-dependent UNG2 turnover. PloS one 37 22292079
2023 Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy. Nature communications 36 37024504
2018 HIV-1 Vpr Reprograms CLR4DCAF1 E3 Ubiquitin Ligase to Antagonize Exonuclease 1-Mediated Restriction of HIV-1 Infection. mBio 36 30352932
2011 VprBP binds full-length RAG1 and is required for B-cell development and V(D)J recombination fidelity. The EMBO journal 35 22157821
2011 The Cullin-RING E3 ubiquitin ligase CRL4-DCAF1 complex dimerizes via a short helical region in DCAF1. Biochemistry 34 21226479
2019 DCAF1 (VprBP): emerging physiological roles for a unique dual-service E3 ubiquitin ligase substrate receptor. Journal of molecular cell biology 33 30590706
2018 Temporal Regulation of ESCO2 Degradation by the MCM Complex, the CUL4-DDB1-VPRBP Complex, and the Anaphase-Promoting Complex. Current biology : CB 30 30100344
2016 DCAF1 controls T-cell function via p53-dependent and -independent mechanisms. Nature communications 30 26728942
2010 The functions of the HIV1 protein Vpr and its action through the DCAF1.DDB1.Cullin4 ubiquitin ligase. Cytokine 29 20347598
2023 Phosphorylation and stabilization of EZH2 by DCAF1/VprBP trigger aberrant gene silencing in colon cancer. Nature communications 28 37069142
2023 Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field. ACS medicinal chemistry letters 27 37465299
2020 A small molecule NRF2 activator BC-1901S ameliorates inflammation through DCAF1/NRF2 axis. Redox biology 26 32171724
2024 Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity. Nature communications 25 39580491
2017 Inhibition of Vpx-Mediated SAMHD1 and Vpr-Mediated Host Helicase Transcription Factor Degradation by Selective Disruption of Viral CRL4 (DCAF1) E3 Ubiquitin Ligase Assembly. Journal of virology 25 28202763
2013 HIV-1 Vpr induces the degradation of ZIP and sZIP, adaptors of the NuRD chromatin remodeling complex, by hijacking DCAF1/VprBP. PloS one 24 24116224
2017 HIV-1 Vpr protein directly loads helicase-like transcription factor (HLTF) onto the CRL4-DCAF1 E3 ubiquitin ligase. The Journal of biological chemistry 23 29079575
2021 DCAF1-targeting microRNA-3175 activates Nrf2 signaling and inhibits dexamethasone-induced oxidative injury in human osteoblasts. Cell death & disease 22 34716304
2018 HIV-1 Vpr hijacks EDD-DYRK2-DDB1DCAF1 to disrupt centrosome homeostasis. The Journal of biological chemistry 22 29724823
2014 The HIV-1 accessory protein Vpr induces the degradation of the anti-HIV-1 agent APOBEC3G through a VprBP-mediated proteasomal pathway. Virus research 21 25200749
2023 Discovery of a Novel DCAF1 Ligand Using a Drug-Target Interaction Prediction Model: Generalizing Machine Learning to New Drug Targets. Journal of chemical information and modeling 20 37350740
2021 VprBP directs epigenetic gene silencing through histone H2A phosphorylation in colon cancer. Molecular oncology 20 34312968
2014 Structural basis of DDB1-and-Cullin 4-associated Factor 1 (DCAF1) recognition by merlin/NF2 and its implication in tumorigenesis by CD44-mediated inhibition of merlin suppression of DCAF1 function. Genes to cells : devoted to molecular & cellular mechanisms 19 24912773
2014 Defining the interactions and role of DCAF1/VPRBP in the DDB1-cullin4A E3 ubiquitin ligase complex engaged by HIV-1 Vpr to induce a G2 cell cycle arrest. PloS one 17 24558487
2010 Merlin's tumor suppression linked to inhibition of the E3 ubiquitin ligase CRL4 (DCAF1). Cell cycle (Georgetown, Tex.) 17 21084862
2018 VprBP (DCAF1) Regulates RAG1 Expression Independently of Dicer by Mediating RAG1 Degradation. Journal of immunology (Baltimore, Md. : 1950) 16 29925675
2015 Tumor suppressor protein Lgl mediates G1 cell cycle arrest at high cell density by forming an Lgl-VprBP-DDB1 complex. Molecular biology of the cell 15 25947136
2014 Structural basis of the binding of Merlin FERM domain to the E3 ubiquitin ligase substrate adaptor DCAF1. The Journal of biological chemistry 15 24706749
2013 Autophagy negatively regulates cancer cell proliferation via selectively targeting VPRBP. Clinical science (London, England : 1979) 15 22963397
2023 VprBP/DCAF1 regulates p53 function and stability through site-specific phosphorylation. Oncogene 14 37041410
2021 HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7. Virology journal 14 33648539
2020 VprBP mitigates TGF-β and Activin signaling by promoting Smurf1-mediated type I receptor degradation. Journal of molecular cell biology 14 31291647
2014 Interactions with DCAF1 and DDB1 in the CRL4 E3 ubiquitin ligase are required for Vpr-mediated G2 arrest. Virology journal 11 24912982
2019 Determinants of lentiviral Vpx-CRL4 E3 ligase-mediated SAMHD1 degradation in the substrate adaptor protein DCAF1. Biochemical and biophysical research communications 10 31003777
2001 VP-RBP, a protein enriched in brain tissue, specifically interacts with the dendritic localizer sequence of rat vasopressin mRNA. The European journal of neuroscience 10 11285008
2024 Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4+ T cells. Nature communications 9 38443376
2024 Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival. Cell death & disease 9 38862475
2023 VprBP/DCAF1 Triggers Melanomagenic Gene Silencing through Histone H2A Phosphorylation. Biomedicines 9 37760992
2022 VPRBP Functions Downstream of the Androgen Receptor and OGT to Restrict p53 Activation in Prostate Cancer. Molecular cancer research : MCR 9 35348747
2022 CircRNA VPRBP inhibits tumorigenicity of cervical cancer via miR-93-5p/FRMD6 axis. Reproductive sciences (Thousand Oaks, Calif.) 9 35501594
2024 CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X. Viruses 8 39205287
2022 The CRL4 E3 ligase Mahjong/DCAF1 controls cell competition through the transcription factor Xrp1, independently of polarity genes. Development (Cambridge, England) 8 36278853
2014 Understanding the molecular manipulation of DCAF1 by the lentiviral accessory proteins Vpr and Vpx. Virology 8 25499532
2023 AKT Phosphorylates FAM13A and Promotes Its Degradation via CUL4A/DDB1/DCAF1 E3 Complex. American journal of respiratory cell and molecular biology 7 36749583
2015 VprBP Is Required for Efficient Editing and Selection of Igκ+ B Cells, but Is Dispensable for Igλ+ and Marginal Zone B Cell Maturation and Selection. Journal of immunology (Baltimore, Md. : 1950) 7 26150531
2024 CRL4DCAF1 ubiquitin ligase regulates PLK4 protein levels to prevent premature centriole duplication. Life science alliance 6 38490717
2002 Sox9 transactivation and testicular expression of a novel human gene, KIAA0800. Journal of cellular biochemistry 6 12111997
2024 DCAF1 interacts with PARD3 to promote hepatocellular carcinoma progression and metastasis by activating the Akt signaling pathway. Journal of experimental & clinical cancer research : CR 5 38711082
2022 DCAF1 inhibits the NF-κB pathway by targeting p65. Immunology letters 5 36055411
2024 The antitumor peptide M1-20 induced the degradation of CDK1 through CUL4-DDB1-DCAF1-involved ubiquitination. Cancer gene therapy 4 39562696
2021 The CRL4VPRBP(DCAF1) E3 ubiquitin ligase directs constitutive RAG1 degradation in a non-lymphoid cell line. PloS one 4 34648572
2021 Binding to DCAF1 distinguishes TASOR and SAMHD1 degradation by HIV-2 Vpx. PLoS pathogens 4 34699574
2018 DCAF1 is involved in HCV replication through regulation of miR-122. Archives of virology 4 29327233
2024 DOT1L/H3K79me2 represses HIV-1 reactivation via recruiting DCAF1. Cell reports 3 38905100
2016 HIV-1 Vpr increases HCV replication through VprBP in cell culture. Virus research 3 27460548
2013 The components of Drosophila histone chaperone dCAF-1 are required for the cell death phenotype associated with rbf1 mutation. G3 (Bethesda, Md.) 3 23893745
2025 CSN6 Promotes Pancreatic Cancer Progression and Gemcitabine Resistance via Antagonizing DCAF1-Mediated Ubiquitination of NPM1. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 41114465
2024 STK39 inhibits antiviral immune response by inhibiting DCAF1-mediated PP2A degradation. Acta pharmaceutica Sinica. B 2 40370558
2022 Identification of DCAF1 by Clinical Exome Sequencing and Methylation Analysis as a Candidate Gene for Autism and Intellectual Disability: A Case Report. Journal of personalized medicine 2 35743672
2015 HIV-1 Vpr suppresses the cytomegalovirus promoter in a CRL4(DCAF1) E3 ligase independent manner. Biochemical and biophysical research communications 2 25704090
2025 OICR-41103 as a chemical probe for the DCAF1 WD40 domain. Communications biology 1 40683980
2024 VprBP regulates osteoclast differentiation via an epigenetic mechanism involving histone H2A phosphorylation. Epigenetics & chromatin 1 39587626
2026 Discovery and Characterization of VPRBP/DCAF1 Kinase Inhibitor Analogs as Microtubular Destabilizing Agents with Potent Antimyeloma Activity. Molecular cancer therapeutics 0 41185616
2026 VprBP drives prostate tumorigenesis by its kinase activity targeting histone H2A. Cell communication and signaling : CCS 0 42192547
2025 DCAF1 promotes the growth and metastasis of pancreatic cancer cells by activating the PTEN/PI3K/Akt signaling pathway. General physiology and biophysics 0 41217229
2023 VprBP/DCAF1 triggers melanomagenic gene silencing through histone H2A phosphorylation. Research square 0 37293029
2023 Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4+ T cells. Research square 0 37645926

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