Affinage

DDB1

DNA damage-binding protein 1 · UniProt Q16531

Length
1140 aa
Mass
127.0 kDa
Annotated
2026-06-09
100 papers in source corpus 54 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDB1 is the central adaptor subunit of the CUL4-RBX1-DDB1 family of cullin-RING E3 ubiquitin ligases (CRL4), bridging the CUL4 scaffold to interchangeable substrate-recruiting receptors and thereby directing ubiquitination of a broad set of substrates governing genome maintenance, cell-cycle control, and signaling (PMID:16964240, PMID:15448697). Structurally, DDB1 adopts an intertwined three-beta-propeller architecture in which the BPA-BPB double-propeller forms a large pocket for substrate-receptor docking while the flexibly attached BPC propeller binds the N-terminus of CUL4A (PMID:16413485, PMID:16964240). A large family of WD40-repeat proteins (DCAFs/DWD proteins) engages the BPA-BPB pocket through a conserved alpha-helical/DWD-box (WDxR) motif, the same structural element exploited by viral hijackers, and these receptors confer substrate specificity on the ligase (PMID:16964240, PMID:19966799, PMID:17079684, PMID:16949367). Through distinct DCAFs, CRL4^DDB1 enforces replication licensing by degrading CDT1 in a PCNA-coupled manner via CDT2, an activity required to prevent re-replication, checkpoint activation, and genome-wide double-strand breaks (PMID:15448697, PMID:16949367, PMID:16482215, PMID:16940174), and it operates within nucleotide excision repair by scaffolding DDB2 to UV-damaged chromatin, where the complex monoubiquitinates histone H2A (PMID:19109893, PMID:16473935, PMID:16951172). DDB1-CUL4 additionally targets diverse regulators including CHK1, p27, TSC2, Merlin, and circadian CRY1 for degradation, and modulates substrate activity by monoubiquitination of p73 and PHGDH (PMID:19276361, PMID:16537899, PMID:18381890, PMID:18332868, PMID:26431207, PMID:23085759, PMID:34720086). In vivo, conditional DDB1 loss triggers aberrant accumulation of cell-cycle regulators, genomic instability, and p53-dependent apoptosis of proliferating progenitors (PMID:17129780, PMID:17301228). The DDB1 scaffold is co-opted by viral proteins—paramyxovirus SV5-V, HBV HBx, and HIV-1 Vpr—to redirect CRL4 against host factors such as STAT1, Smc5/6, and UNG2 (PMID:16413485, PMID:27571178, PMID:12388698, PMID:15767425), and it is exploited pharmacologically by IMiD molecular glues acting through the DCAF CRBN and by molecular glues and covalent recruiters that engage DDB1 directly for targeted protein degradation (PMID:25043012, PMID:32804079, PMID:38192078).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 Medium

    Established that DDB1 is functionally required for a viral protein to reprogram host protein degradation, the first hint that DDB1 serves as an adaptor for ubiquitin-mediated turnover.

    Evidence V protein mutagenesis and siRNA depletion of DDB1 with IFN-signaling and STAT1 degradation readouts

    PMID:12388698

    Open questions at the time
    • Did not define the cullin/ligase machinery DDB1 recruits
    • DDB1's endogenous cellular substrates unaddressed
  2. 2004 High

    Defined DDB1 as the adaptor bridging an endogenous substrate (CDT1) to the CUL4A scaffold, establishing its core role in a cellular E3 ligase.

    Evidence Reciprocal co-IP, in vitro binding and ubiquitination reconstitution, and siRNA knockdown in human cells

    PMID:15448697

    Open questions at the time
    • How DDB1 recognizes diverse substrates beyond CDT1 unknown
    • No structural basis for adaptor function
  3. 2006 High

    Resolved the three-propeller architecture of DDB1 and demonstrated a division of labor—BPC binds CUL4A while the BPA-BPB pocket receives substrate receptors—explaining how DDB1 functions as a modular adaptor and how viral helices hijack it.

    Evidence X-ray crystallography of apo DDB1 and DDB1-CUL4A-ROC1 complexes with SV5-V; TAP-MS of DDB1/CUL4A complexes

    PMID:16413485 PMID:16964240

    Open questions at the time
    • Conformational dynamics of BPC docking during catalysis not resolved
    • Full DCAF repertoire not yet enumerated
  4. 2006 High

    Systematically identified the DCAF/DWD family and the conserved WDxR/DWD-box motif as the universal substrate-receptor interface, explaining how one adaptor generates a combinatorial ligase family.

    Evidence Mass-spectrometry proteomics, yeast two-hybrid, and motif mutagenesis identifying ~15-18 DDB1-CUL4-associated WD40 factors

    PMID:16949367 PMID:17079684

    Open questions at the time
    • Substrate of most DCAFs unassigned at the time
    • Rules governing receptor exchange on DDB1 unknown
  5. 2006 High

    Established the genome-maintenance logic of CRL4^DDB1: PCNA-coupled CDT2 degradation of CDT1 prevents re-replication, with DDB1 loss causing checkpoint activation and DNA breaks.

    Evidence siRNA knockdown, Xenopus extract reconstitution, mutational dissection of CDT1 degrons, and γH2AX/epistasis assays

    PMID:16407242 PMID:16482215 PMID:16861906 PMID:16940174 PMID:16949367

    Open questions at the time
    • Distinction between SCF-Skp2 and CRL4 redundancy in vivo incompletely mapped
    • PCNA-degron coupling mechanism still being refined
  6. 2006 High

    Defined DDB1's role in nucleotide excision repair, scaffolding the damage sensor DDB2 to UV lesions and enabling histone H2A monoubiquitination at damaged chromatin.

    Evidence In vitro damaged-DNA binding with purified DDB1-DDB2, endogenous complex biochemistry in UV-irradiated/XP-E cells, fractionation and repair assays

    PMID:16223728 PMID:16473935 PMID:16951172

    Open questions at the time
    • Whether H2A ubiquitination directly drives repair versus chromatin remodeling unresolved
    • CPD-versus-6-4PP repair specificity mechanism unclear
  7. 2006 Medium

    Demonstrated that CRL4^DDB1 reaches beyond degradation into chromatin regulation by engaging histone methylation machinery (WDR5, EED) and influencing H3K4/H3K27 methylation.

    Evidence Co-IP, siRNA knockdown with methylation readouts, and methylated-nucleosome pull-down

    PMID:17041588

    Open questions at the time
    • Direct ubiquitination substrate within the methylation complexes not defined
    • Single-lab evidence
  8. 2008 High

    Showed the structural element used by cellular DCAFs is mimicked by HBV HBx, unifying viral and host assembly of CRL4 complexes and explaining HBx-dependent viral replication.

    Evidence X-ray crystallography of DDB1-HBx with structure-based mutagenesis; HBx point-mutant complementation and RNAi in HBV replication assays

    PMID:15767425 PMID:19966799

    Open questions at the time
    • Identity of the host substrate degraded by HBx-DDB1 not defined here
    • Mechanism linking degradation to replication enhancement incomplete
  9. 2008 High

    Extended the substrate repertoire of CRL4^DDB1 to growth and tumor-suppressor pathways through specific DCAFs (FBW5→TSC2, VprBP→Merlin), linking DDB1 to mTOR and ERK/Rac signaling.

    Evidence Co-IP, in vitro/in vivo ubiquitination, siRNA, and Drosophila genetics

    PMID:18332868 PMID:18381890

    Open questions at the time
    • Physiological signals triggering these degradation events partly defined
    • In vivo contribution to tumor suppression untested
  10. 2007 High

    Established HIV-1 Vpr as a DDB1-CUL4 hijacker acting through DCAF1/VprBP to drive G2 arrest and degrade host factors, generalizing viral exploitation of the scaffold.

    Evidence TAP-MS, reciprocal co-IP, siRNA epistasis, proteasome inhibition, and cell-cycle/apoptosis assays across multiple labs

    PMID:17314515 PMID:17360488 PMID:17609381 PMID:17620334 PMID:17626091 PMID:17630831

    Open questions at the time
    • Full set of Vpr-redirected substrates not exhausted
  11. 2006 High

    Genetic ablation in mouse tissues established the in vivo physiological requirement for DDB1 in proliferating cells, where its loss causes cell-cycle regulator accumulation, genomic instability, and p53-driven apoptosis.

    Evidence Conditional knockout in brain, lens, and epidermis with histology, marker analysis, and p53 genetic epistasis

    PMID:17129780 PMID:17301228

    Open questions at the time
    • Which specific substrate accumulation is primary driver of apoptosis not pinpointed
    • Tissue-specific differences in critical substrates unresolved
  12. 2009 High

    Identified CHK1 as a CRL4^DDB1 target, embedding DDB1 in a DNA-damage-response feedback circuit where activated CHK1 is downregulated and USP1 opposes this turnover.

    Evidence Co-IP, in vitro ubiquitination, siRNA, and stability assays; USP1 epistasis under genotoxic stress

    PMID:19276361 PMID:21389083

    Open questions at the time
    • Identity of the CHK1-specific DCAF not defined
    • Quantitative impact on checkpoint timing unclear
  13. 2013 Medium

    Expanded CRL4^DDB1 function into circadian, metabolic, and telomere regulation, and showed it can modulate activity (monoubiquitination) rather than only trigger degradation.

    Evidence In vitro/in vivo ubiquitination, site mutagenesis, circadian reporters, conditional mouse models, and kinase assays linking DDB1 to CRY1, raptor, TERT and FOXO1/gluconeogenesis

    PMID:23297343 PMID:23362280 PMID:26431207 PMID:28790135

    Open questions at the time
    • Several substrate links rest on single-lab evidence
    • Crosstalk between these pathways in vivo not integrated
  14. 2014 High

    Revealed how small molecules exploit the DDB1 scaffold: IMiDs binding the DCAF CRBN reprogram substrate specificity, simultaneously recruiting neo-substrates (IKZF1/3) and blocking endogenous ones.

    Evidence X-ray crystallography of DDB1-CRBN with three IMiDs, unbiased substrate screen, mutagenesis, and ubiquitination assays in myeloma models

    PMID:25043012 PMID:25108355

    Open questions at the time
    • Generality of glue-induced neo-substrate recruitment beyond CRBN not yet shown here
  15. 2020 High

    Demonstrated that molecular glues and covalent recruiters can engage DDB1 directly, bypassing DCAF receptors to create neo-substrate ligases, validating DDB1 itself as a targeted-degradation platform.

    Evidence HTS, genetic screens, and biochemical reconstitution for HQ461/CDK12-CCNK; cysteine chemoproteomics identifying DDB1 C173 recruiter used to build BRD4/AR PROTACs

    PMID:32804079 PMID:38192078

    Open questions at the time
    • Structural basis of direct DDB1-glue neo-substrate ternary complexes not fully resolved
    • Selectivity and in vivo efficacy of DDB1 recruiters early-stage

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how DDB1 dynamically selects among its many competing DCAF receptors and how this exchange is regulated by post-translational modification across distinct cellular states.
  • No quantitative model of DCAF competition for the BPA-BPB pocket
  • Regulatory roles of DDB1 phosphorylation/acetylation only sketched (e.g. SIRT7, PKA in Drosophila)
  • Substrate priority during simultaneous demands of replication, repair, and signaling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-69306 DNA Replication 4 R-HSA-73894 DNA Repair 4 R-HSA-4839726 Chromatin organization 3 R-HSA-9909396 Circadian clock 3
Partners
CDT1CRBNCUL4ADCAF1/VPRBPDCAF2/CDT2DDB2FBW5RBX1
Complex memberships
CUL4A-RBX1-DDB1 (CRL4) E3 ubiquitin ligaseCUL4B-DDB1-DCAF1 E3 ubiquitin ligaseDDB1-DDB2 (UV-DDB) complexEDD-DDB1-VprBP E3 ligase

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Crystal structure of DDB1 reveals an intertwined three-propeller (BPA, BPB, BPC) architecture: two tightly coupled beta-propellers (BPA-BPB) form a double-propeller fold with a large pocket, while a third beta-propeller (BPC) is flexibly attached and docks DDB1 to the N-terminus of CUL4A. The SV5 V protein inserts a helix into the BPA-BPB double-propeller pocket to hijack the complex. X-ray crystallography of DDB1 alone and in complex with paramyxovirus SV5-V protein Cell High 16413485
2006 DDB1 uses its BPC beta-propeller domain for CUL4A scaffold binding and its BPA-BPB double-propeller fold for substrate presentation. A family of WD40-repeat proteins (DCAFs) directly binds the double-propeller fold of DDB1 and serves as the substrate-recruiting module of the CUL4A-RBX1-DDB1 E3 ligase. X-ray crystallography of the virally-hijacked DDB1-CUL4A-ROC1 complex; tandem-affinity purification of DDB1/CUL4A complexes followed by mass spectrometry Nature High 16964240
2008 Crystal structures of the DDB1-DDB2 complex alone and bound to UV-damaged DNA (6-4PP or abasic site) show that the lesion is held exclusively by the WD40 domain of DDB2. A DDB2 hairpin inserts into the minor groove, extrudes the photodimer into a binding pocket, and kinks the duplex ~40°. DDB1 scaffolds DDB2 and the associated CUL4 ubiquitin ligase to damaged chromatin. X-ray crystallography of DDB1-DDB2 complex alone and with damaged DNA substrates Cell High 19109893
2009 Crystal structure of DDB1 in complex with hepatitis B virus X protein (HBx) reveals that HBx binds DDB1 through an alpha-helical motif that is also present in SV5-V protein and in cellular DCAFs, identifying a common structural element for assembly of CUL4-DDB1 E3 complexes. X-ray crystallography of DDB1-HBx complex; structure-based mutagenesis and functional analysis Nature structural & molecular biology High 19966799
2014 Crystal structure of DDB1-CRBN in complex with thalidomide, lenalidomide, and pomalidomide establishes that CRBN is a DCAF substrate receptor within CRL4^CRBN and enantioselectively binds IMiDs. IMiDs promote ubiquitination of IKZF1/IKZF3 while blocking endogenous substrate MEIS2 from binding, demonstrating dual modulation of E3 ligase substrate specificity. X-ray crystallography; unbiased substrate screen; functional ubiquitination assays Nature High 25043012
2014 Crystal structure of human CRBN-DDB1-lenalidomide complex shows a hydrophobic pocket in the thalidomide-binding domain (TBD) of CRBN accommodates the glutarimide moiety of lenalidomide. Site-directed mutagenesis confirmed key drug-binding residues are critical for antiproliferative effects. X-ray crystallography; site-directed mutagenesis in lentiviral myeloma models Nature structural & molecular biology High 25108355
2016 Crystal structure of DDB1-DCAF1-HIV-1 Vpr-UNG2 complex reveals how Vpr engages DCAF1 to create a binding interface for UNG2 recruitment, targeting UNG2 for CRL4-mediated degradation via molecular mimicry of DNA by a Vpr variable loop. X-ray crystallography of the quaternary complex Nature structural & molecular biology High 27571178
2004 DDB1 associates stoichiometrically with CUL4A in vivo and binds directly to CDT1 in vitro; ectopic DDB1 bridges CDT1 to CUL4A in vivo. Silencing DDB1 prevents UV-induced CDT1 degradation in vivo and blocks CUL4A-mediated CDT1 ubiquitination in vitro, establishing DDB1 as the adaptor targeting CDT1 for CUL4A-dependent ubiquitination after UV damage. Co-immunoprecipitation; in vitro binding assay; in vitro ubiquitination assay; siRNA knockdown Nature cell biology High 15448697
2006 DDB1 functions as a linker between CUL4A and substrate-recruiting WD40 proteins (DWD proteins) via a conserved DWD box motif. Fifteen DWD proteins were shown to bind DDB1-CUL4A, and the DWD box is necessary and sufficient for DDB1 binding. Yeast two-hybrid; co-immunoprecipitation; motif mutagenesis Genes & development High 17079684
2006 Eighteen DDB1- and CUL4-associated factors (DCAFs) were identified, including 14 WD40 proteins. DCAFs interact with DDB1 through a conserved 'WDXR' motif. DCAF2/Cdt2 recruits Cdt1 to CUL4-DDB1 for ubiquitylation at replication forks via PCNA, and Cdt2 depletion causes rereplication. Mass spectrometry proteomics; co-immunoprecipitation; Xenopus egg extract reconstitution; siRNA knockdown Molecular cell High 16949367
2006 The DDB1-CUL4A^DDB2 ubiquitin ligase monoubiquitinates histone H2A in native chromatin at UV-damaged DNA sites. DDB2 mutations (XP-E) impair E3 ligase activity and reduce H2A monoubiquitination after UV, which is associated with decreased global genome NER. Co-immunoprecipitation of endogenous complexes from UV-irradiated cells; comparison with XP-E mutant cells; chromatin fractionation Proceedings of the National Academy of Sciences of the United States of America High 16473935
2006 CUL4-DDB1 complexes interact with WD40 proteins WDR5 and EED, components of histone methylation complexes. Inactivation of CUL4 or DDB1 impairs histone H3K4 and H3K27 methylation. CUL4A-DDB1 interacts with H3-methylated mononucleosomes. Co-immunoprecipitation; siRNA knockdown with histone methylation readouts; chromatin pull-down Nature cell biology Medium 17041588
2006 DDB1 knockdown in human cells impairs repair of UV-induced cyclobutane pyrimidine dimers (CPD) but not 6-4 photoproducts. Upon UV irradiation, DDB1 translocates from loosely to tightly bound chromatin fraction in a DDB2-dependent manner. DDB1 is required for UV-induced DDB2 ubiquitylation and degradation, and bridges DDB2 to CUL4A at damage sites. siRNA knockdown; nuclear fractionation; immunofluorescence at laser-induced damage foci; repair assays Cancer research Medium 16951172
2006 DDB1 depletion causes accumulation of CDT1 protein and DNA re-replication, activates ATM/ATR checkpoints, and leads to genome-wide DNA double-strand breaks during S-phase. Co-depletion of CDT1 partially suppresses these phenotypes, placing CDT1 regulation downstream of DDB1 in genome maintenance. siRNA knockdown; flow cytometry; γH2AX immunofluorescence; epistasis by co-depletion Molecular and cellular biology Medium 16940174
2006 DDB1 dynamically accumulates at UV-damaged DNA sites in living cells. Its binding to damaged DNA is transient and requires DDB2 but not CUL4A. UV-dependent degradation of DDB2 releases DDB1 from continuous association with unrepaired DNA, making DDB1 available for other functions. Live-cell fluorescence microscopy with fluorescently tagged DDB1; FRAP; cell lines with DDB2 knockdown or DDB2 mutations Molecular and cellular biology Medium 18936169
2005 Purified DDB1-DDB2 complex binds cyclobutane pyrimidine dimers with ~6-fold higher affinity than undamaged DNA, as well as 6-4 photoproducts, abasic sites, and 2-3 bp mismatches. DDB acts as a conformational sensor rather than lesion-specific detector. In vitro binding assays with highly purified DDB1-DDB2 complex and defined damaged DNA substrates; quantitative affinity measurements The Journal of biological chemistry High 16223728
2006 DDB1-CUL4 E3 ligase targets CDT1 for degradation during S phase and after DNA damage through two distinct E3 ligases: DDB1-CUL4 recognizes the N-terminal 10 amino acids of CDT1 and requires PCNA, while SCF-Skp2 recognizes a CDK-phosphorylated Cy-motif. PCNA is essential for CUL4- but not SKP2-directed CDT1 degradation. Mutational analysis of CDT1 degradation signals; siRNA co-depletion of Skp2 and Cul4; co-immunoprecipitation; cell cycle analysis The EMBO journal High 16482215
2006 PCNA interacts with CDT1 and is required for CUL4-DDB1-mediated N-terminal ubiquitination of CDT1 in S phase and after UV irradiation. Overexpression of the PCNA-inhibitory domain from p21 or p57 blocks CDT1 degradation. Deletion of Ddb1 in fission yeast accumulates CDT1 even without DNA damage. In vivo ubiquitination assay; siRNA knockdown of PCNA; gel filtration co-elution; PCNA inhibitory domain overexpression; fission yeast genetics The Journal of biological chemistry Medium 16407242
2006 CUL4A associates with Skp2 and DDB1 forms a physical complex with CUL4A, Skp2, and the COP9 signalosome. DDB1 knockdown, CSN1 knockdown, or CUL4A knockdown causes p27Kip1 accumulation. DDB1 overexpression reduces p27Kip1 stability via CUL4A and the COP9 signalosome. siRNA knockdown; co-immunoprecipitation; pulse-chase; overexpression Molecular and cellular biology Medium 16537899
2009 DDB1 interacts with CHK1 and is part of a CUL4A/CUL4B E3 ligase complex that negatively regulates CHK1 protein stability. CHK1 ubiquitination is Cul4A/DDB1-dependent in vitro and in vivo, and CHK1 is stabilized in Cul4A/DDB1-deficient cells. CHK1 phosphorylation and replication stress enhance DDB1-CHK1 interaction. Co-immunoprecipitation; in vitro ubiquitination assay; siRNA knockdown; protein stability assays Cancer research High 19276361
2011 USP1 deubiquitinase counteracts DDB1-dependent degradation of phosphorylated CHK1. USP1 depletion stimulates DDB1-dependent degradation of phospho-CHK1, establishing a negative feedback circuit in the DNA damage response where activated CHK1 is downregulated via DDB1-mediated ubiquitination. siRNA knockdown of USP1; co-immunoprecipitation; CHK1 stability measurements in response to genotoxic stress Human molecular genetics Medium 21389083
2007 HIV-1 Vpr binds DDB1 through DCAF1/VprBP, and Vpr-mediated G2 arrest requires DDB1, CUL4A, and DCAF1. Tandem affinity purification identified DDB1, VPRBP, and CUL4A as Vpr-associated proteins. Proteasome inhibition abolishes Vpr-induced G2 arrest, consistent with ubiquitin ligase-mediated target degradation. Tandem affinity purification/mass spectrometry; co-immunoprecipitation; siRNA knockdown; cell cycle analysis by flow cytometry; proteasome inhibitor experiments Journal of virology High 17314515 17609381 17620334 17626091 17630831
2007 HIV-1 Vpr binding to DDB1 (via DDB1-CUL4 ubiquitin ligase interaction) mediates Vpr-induced apoptosis and UNG2/SMUG1 degradation, and impairs UV-damaged DNA repair. DDB1 was identified as the predominant Vpr-interacting cellular protein by tandem affinity purification and mass spectrometry. Tandem affinity purification/mass spectrometry; co-immunoprecipitation; siRNA knockdown; functional assays for apoptosis and UNG2 degradation Proceedings of the National Academy of Sciences of the United States of America Medium 17360488
2002 DDB1 (p127) is essential for SV5 V protein-mediated STAT1 degradation. V protein mutants that fail to bind DDB1 cannot block IFN signaling. siRNA depletion of DDB1 prevents STAT1 degradation and restores IFN signaling. STAT1 degradation is independent of DDB2. Protein-protein interaction assays; V protein mutagenesis; siRNA knockdown; IFN signaling assays Journal of virology Medium 12388698
2005 SV5 V protein acts as an adaptor linking DDB1 (via its N-terminal domain) to STAT2/STAT1 heterodimers, assembling a DDB1/CUL4A-containing ubiquitin ligase complex that ubiquitinates STAT1. V binds DDB1 and STAT2 independently; STAT1-STAT2 interaction is V-independent. Direct protein-protein interaction assays (GST pulldown, co-IP); yeast two-hybrid; ubiquitination assay with CUL4A components Journal of virology Medium 16227264
2008 FBW5, a DWD-box WD40 protein, binds DDB1 and recruits TSC2 to the DDB1-CUL4-ROC1 E3 ubiquitin ligase for ubiquitination and proteasomal degradation. TSC1 co-expression with TSC2 protects TSC2 from FBW5-mediated degradation. Drosophila Cul4/Ddb1 mutations cause Gigas/TSC2 accumulation. Co-immunoprecipitation; in vitro ubiquitination; siRNA knockdown; overexpression; Drosophila genetics Genes & development High 18381890
2006 L2DTL/CDT2 associates with CUL4, DDB1, and PCNA in vivo. Loss of L2DTL suppresses CDT1 proteolysis after DNA damage. In vivo, inactivation of L2DTL causes dissociation of DDB1 from the CUL4 complex, and PCNA interacts with CDT1 through the same region required for CUL4-mediated degradation. Anti-CUL4 affinity chromatography/mass spectrometry; co-immunoprecipitation; siRNA knockdown in Drosophila S2 cells and human cells Cell cycle Medium 16861906
2012 EZH2 methylates non-histone substrate RORα, generating a monomethyl degron recognized by the DCAF1 chromo domain. The DCAF1/DDB1/CUL4 E3 complex then ubiquitinates the monomethylated substrate for degradation. Mutations in the DCAF1 chromo domain abolish binding to monomethylated substrates. In vitro methylation assay; molecular modeling; binding affinity studies; DCAF1 chromo domain mutagenesis; co-immunoprecipitation Molecular cell Medium 23063525
2008 VprBP acts as the substrate receptor that recruits Merlin (NF2 tumor suppressor) to the ROC1-CUL4A-DDB1 E3 ubiquitin ligase. Serum stimulation induces Merlin recruitment, polyubiquitination, and proteasomal degradation. VprBP depletion stabilizes Merlin and inhibits ERK/Rac activation. Co-immunoprecipitation; siRNA knockdown; in vivo ubiquitination assay; serum stimulation experiments Oncogene Medium 18332868
2013 DDB1-CUL4 E3 ubiquitin ligase monoubiquitylates raptor, a component of mTORC1. UCH-L1 deubiquitinase disrupts the DDB1-CUL4/raptor complex and counteracts DDB1-CUL4-mediated raptor ubiquitination, promoting mTORC1 dissolution and secondary mTORC2 increase. Co-immunoprecipitation; ubiquitination assay; UCH-L1 transgenic and knockout mouse models; mTOR complex assembly analysis Molecular and cellular biology Medium 23297343
2006 Conditional deletion of DDB1 in mouse brain and lens causes selective apoptosis of proliferating neuronal progenitor and lens epithelial cells, preceded by aberrant accumulation of cell cycle regulators and genomic instability. Cell death is partially rescued by co-deletion of p53, placing p53 activation downstream of DDB1 loss. Conditional knockout mouse genetics; histology; immunohistochemistry; p53 genetic epistasis Cell High 17129780
2007 Tissue-specific deletion of DDB1 in mouse epidermis causes accumulation of c-Jun and p21Cip1, G2/M arrest, selective apoptosis of proliferating progenitor cells, and near-complete loss of epidermis and hair follicles. Co-deletion of p53 partially rescues progenitors but permits aneuploidy accumulation. Conditional knockout mouse genetics; immunohistochemistry; cell cycle analysis; p53 epistasis Proceedings of the National Academy of Sciences of the United States of America High 17301228
2005 HBx requires DDB1 binding for both its cell-killing activity and its ability to stimulate HBV genome replication. DDB1-binding-deficient HBx point mutants fail to complement HBx-deficient HBV replication. DDB1 depletion by RNAi specifically compromises wild-type HBV replication. HBx fused directly to DDB1 rescues replication activity. HBx point mutagenesis; DDB1 fusion protein; RNAi depletion; plasmid-based HBV replication assay Journal of virology Medium 15767425
2003 In fission yeast, Ddb1 is required for proteolysis of Spd1 (a ribonucleotide reductase inhibitor) in S phase and after DNA damage. Deletion of spd1 suppresses the growth defects and DNA damage sensitivity of Δddb1 cells, placing Spd1 as a key substrate downstream of Ddb1 in genome stability. Fission yeast genetics; protein stability assays; epistasis by double-mutant analysis The Journal of biological chemistry Medium 14701809
2013 Dyrk2-associated EDD-DDB1-VprBP E3 ligase mediates ubiquitin-dependent degradation of TERT (telomerase catalytic subunit). Dyrk2 phosphorylates TERT; phosphorylated TERT is then recognized by the VprBP substrate receptor of the EDD-DDB1-VprBP complex for ubiquitination and degradation at G2/M. Co-immunoprecipitation; in vivo ubiquitination assay; siRNA knockdown; kinase assay; cell cycle analysis The Journal of biological chemistry Medium 23362280
2013 Ramshackle (Brwd3/BRWD3) functions as a DCAF within a CRL4 complex (CUL4-ROC1-DDB1-BRWD3) that mediates light-dependent ubiquitylation of Drosophila cryptochrome (dCRY). Light induces binding of dCRY to the complex, leading to dCRY ubiquitylation and degradation. RNAi screen in S2 cells; co-immunoprecipitation; ubiquitylation assay; light-dependent complex formation Proceedings of the National Academy of Sciences of the United States of America Medium 23479607
2015 CUL4A-DDB1-CDT2 E3 ligase ubiquitinates CRY1 at lysine 585 and promotes its degradation in vitro and in vivo. Depletion of DDB1, CDT2, or PCNA stabilizes CRY1 in cells and mouse liver. CRY1-K585A mutant is resistant to DDB1-mediated ubiquitination. DDB1 depletion enhances circadian Bmal1 promoter oscillatory amplitude. In vitro ubiquitination assay; siRNA knockdown; site-directed mutagenesis; circadian reporter assay; mouse liver Ddb1 deletion PloS one Medium 26431207
2017 DDB1-CUL4A ubiquitin E3 ligase degrades CRY1, thereby stabilizing FOXO1 and promoting hepatic gluconeogenesis. Hepatocyte-specific Ddb1 deletion impairs gluconeogenesis and protects from diet-induced hyperglycemia in mice. Mechanistically, DDB1 enhances FOXO1 stability by degrading CRY1, a known suppressor of FOXO1. Hepatocyte-specific conditional knockout mouse; high-fat diet experiments; gluconeogenesis assays; protein stability measurements Diabetes Medium 28790135
2017 SIRT7 deacetylates DDB1 at lysine 1121. The deacetylation-mimicking K1121R-DDB1 mutant shows reduced binding to DCAF1, leading to reduced CUL4B/DDB1/DCAF1 E3 ligase activity and increased TR4 nuclear receptor stability. In vitro deacetylation assay; co-immunoprecipitation; mutagenesis; target gene expression analysis Biochemical and biophysical research communications Medium 28623141
2009 WDR-23, a WD40 protein, interacts with CUL-4/DDB-1 ubiquitin ligase to repress SKN-1 protein levels, nuclear accumulation, and transcriptional activity in C. elegans, presumably by targeting SKN-1 for proteasomal degradation. WDR-23 acts downstream of p38 MAPK, GSK-3, and insulin-like receptor pathways on SKN-1. Genetic screen; co-immunoprecipitation; RNAi; fluorescence microscopy; epistasis analysis Molecular and cellular biology Medium 19273594
2009 DDB1-CUL4 and MLL1 mediate oncogenic Ras-induced p16INK4a activation. DDB1 silencing blocks Ras-induced p16 induction. CUL4A directly binds the p16 locus. DDB1-CUL4 acts upstream of MLL1-mediated H3K4 methylation at the p16 locus. siRNA knockdown; ChIP; co-immunoprecipitation; Ras-induced senescence model Cancer research Medium 19208841
2012 The CUL4A/DDB1 E3 ligase monoubiquitylates p73 through direct DDB1-p73 binding. Monoubiquitylation does not affect p73 stability but negatively regulates p73 transcriptional activity. DDB1 depletion induces p73 target gene expression in a p53-independent manner. Co-immunoprecipitation; in vivo ubiquitination assay; siRNA knockdown; transcriptional reporter assays Oncogene Medium 23085759
2020 Molecular glue HQ461 promotes a direct interaction between CDK12 and DDB1-CUL4-RBX1 E3 ubiquitin ligase, bypassing the requirement for a substrate-specific DCAF receptor. This interaction leads to polyubiquitination and degradation of Cyclin K (CCNK), reduced CDK12 substrate phosphorylation, and cell death. High-throughput screening; loss-of-function and gain-of-function genetic screening; biochemical reconstitution; co-immunoprecipitation; SAR analysis eLife High 32804079
2021 CUL4A-DDB1-based E3 ligase monoubiquitinates PHGDH at lysine 146, enhancing its enzymatic activity by promoting tetrameric formation via DnaJA1 chaperone recruitment. This increases serine, glycine, and SAM levels, upregulating adhesion genes via H3K4me3, thereby promoting CRC metastasis. In vivo and in vitro ubiquitination assays; co-immunoprecipitation; mutagenesis; metabolomics; ChIP The Journal of clinical investigation Medium 34720086
2022 CUL4A-DDB1-WDFY1 E3 ubiquitin ligase complex initiates lysophagy by ubiquitinating LAMP2 on damaged lysosomes. WDFY1 serves as the DCAF substrate receptor. Loss of CUL4A, DDB1, or WDFY1 impairs lysophagy and clearance of damaged lysosomes. Proteomic analysis using transfection reagent-coated beads; co-immunoprecipitation; siRNA knockdown; autophagy/lysosome damage assays Cell reports Medium 36103833
2024 Cysteine chemoproteomic screening identified a covalent recruiter targeting C173 on DDB1. This DDB1 recruiter was exploited to develop PROTACs against BRD4 and androgen receptor. BRD4 PROTAC selectively degrades the short BRD4 isoform in a proteasome-, NEDDylation-, and DDB1-dependent manner, demonstrating DDB1 can be directly exploited for targeted protein degradation. Activity-based protein profiling; cysteine chemoproteomic screening; PROTAC development; siRNA knockdown; degradation assays ACS chemical biology Medium 38192078
2018 The Cul4-DDB1-Gβ E3 ubiquitin ligase complex ubiquitylates Smoothened (Smo) in Drosophila, promoting its internalization and degradation. Smo recruits Cul4-DDB1 through the β subunit of trimeric G protein. Hedgehog signaling dissociates Cul4-DDB1 from Smo by PKA-mediated phosphorylation of DDB1, disrupting its interaction with Gβ. Co-immunoprecipitation; in vivo ubiquitination assay; phosphorylation assay; genetic inactivation of Cul4-DDB1; immunofluorescence for Smo surface expression Journal of cell science Medium 29930086
2016 DCAF7 is a specificity factor for the CUL4-DDB1 complex that binds DNA ligase I and targets it for ubiquitylation. Three ubiquitylation sites on DNA ligase I were mapped. Knockdown of DCAF7 reduces DNA ligase I degradation upon inhibition of proliferation. Replacement of ubiquitylated lysines reduces in vitro ubiquitylation by CUL4-DDB1-DCAF7. Proteomic ubiquitylation site mapping; co-immunoprecipitation; in vitro ubiquitylation assay; siRNA knockdown; mutagenesis The Journal of biological chemistry Medium 27573245
2018 DCAF11 (DDB1 and CUL4-associated factor 11) is the substrate receptor of CRL4 that binds phosphorylated SLBP (Stem-loop binding protein) and mediates its degradation at the end of S phase. DCAF11 cannot bind the non-phosphorylatable T61A-SLBP mutant. DCAF11 and Cul4A co-immunoprecipitate with SLBP. Pull-down with phosphorylated SLBP fragment; co-immunoprecipitation; siRNA and overexpression; cell viability assay Cell cycle Medium 27254819
2018 NTZ (nitazoxanide) inhibits the HBx-DDB1 protein-protein interaction, restoring Smc5/6 protein levels and suppressing HBV transcription and protein production in primary hepatocytes naturally infected with HBV. Split luciferase assay for HBx-DDB1 interaction; compound screening; Smc5/6 protein level measurement; viral transcription assays in primary hepatocytes and HBV minicircle system Cellular and molecular gastroenterology and hepatology Medium 30704981

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 870 25043012
2006 Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature 586 16964240
2006 A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Molecular cell 540 16949367
2014 Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nature structural & molecular biology 420 25108355
2007 DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Molecular cell 399 17588513
2006 CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nature cell biology 373 17041588
2008 Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex. Cell 353 19109893
2006 Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. The EMBO journal 328 16482215
2004 Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nature cell biology 316 15448697
2006 DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes & development 288 17079684
2006 The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. Proceedings of the National Academy of Sciences of the United States of America 274 16473935
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
2006 Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell 221 16413485
2012 EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Molecular cell 208 23063525
2006 PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. The Journal of biological chemistry 206 16407252
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
2009 A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery. Nature structural & molecular biology 189 19966799
2009 The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans. Molecular and cellular biology 167 19273594
2007 HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1. Proceedings of the National Academy of Sciences of the United States of America 167 17360488
2020 Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation. eLife 166 32804079
2007 HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase. PLoS pathogens 166 17630831
2008 Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction. PLoS pathogens 159 18451984
2006 L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage. Cell cycle (Georgetown, Tex.) 153 16861906
2008 WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase. Genes & development 142 18381890
2005 Hepatitis B virus X protein stimulates viral genome replication via a DDB1-dependent pathway distinct from that leading to cell death. Journal of virology 139 15767425
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
1995 Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein. Genomics 135 8530102
2006 Deletion of DDB1 in mouse brain and lens leads to p53-dependent elimination of proliferating cells. Cell 134 17129780
2005 DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA. The Journal of biological chemistry 129 16223728
2006 L2DTL/CDT2 and PCNA interact with p53 and regulate p53 polyubiquitination and protein stability through MDM2 and CUL4A/DDB1 complexes. Cell cycle (Georgetown, Tex.) 114 16861890
2009 DDB1 targets Chk1 to the Cul4 E3 ligase complex in normal cycling cells and in cells experiencing replication stress. Cancer research 110 19276361
2007 DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest. Journal of virology 109 17626091
2007 Stealing the spotlight: CUL4-DDB1 ubiquitin ligase docks WD40-repeat proteins to destroy. Cell division 105 17280619
2018 Inhibition of HBV Transcription From cccDNA With Nitazoxanide by Targeting the HBx-DDB1 Interaction. Cellular and molecular gastroenterology and hepatology 101 30704981
2006 An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage. The Journal of biological chemistry 99 16407242
2011 Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions. The international journal of biochemistry & cell biology 97 21959250
2005 Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1. Journal of virology 97 16227264
2002 The p127 subunit (DDB1) of the UV-DNA damage repair binding protein is essential for the targeted degradation of STAT1 by the V protein of the paramyxovirus simian virus 5. Journal of virology 96 12388698
2006 Cul4A and DDB1 associate with Skp2 to target p27Kip1 for proteolysis involving the COP9 signalosome. Molecular and cellular biology 95 16537899
2021 Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine. The Journal of clinical investigation 88 34720086
2008 Rtt101 and Mms1 in budding yeast form a CUL4(DDB1)-like ubiquitin ligase that promotes replication through damaged DNA. EMBO reports 86 18704118
2006 DNA damage binding protein component DDB1 participates in nucleotide excision repair through DDB2 DNA-binding and cullin 4A ubiquitin ligase activity. Cancer research 85 16951172
2005 Ddb1 controls genome stability and meiosis in fission yeast. Genes & development 84 15805471
2008 Altered plastid levels and potential for improved fruit nutrient content by downregulation of the tomato DDB1-interacting protein CUL4. The Plant journal : for cell and molecular biology 83 18363785
2005 Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase. The EMBO journal 83 16252005
2016 The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction. Nature structural & molecular biology 82 27571178
2006 DDB1 maintains genome integrity through regulation of Cdt1. Molecular and cellular biology 79 16940174
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
2006 DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1. EMBO reports 78 17039252
2012 Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication. Virology 75 22342275
2004 The tomato homolog of the gene encoding UV-damaged DNA binding protein 1 (DDB1) underlined as the gene that causes the high pigment-1 mutant phenotype. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 70 14968305
2013 Ubiquitin hydrolase UCH-L1 destabilizes mTOR complex 1 by antagonizing DDB1-CUL4-mediated ubiquitination of raptor. Molecular and cellular biology 68 23297343
2015 Ubiquitin-conjugated degradation of golden 2-like transcription factor is mediated by CUL4-DDB1-based E3 ligase complex in tomato. The New phytologist 63 26352615
2013 Ramshackle (Brwd3) promotes light-induced ubiquitylation of Drosophila Cryptochrome by DDB1-CUL4-ROC1 E3 ligase complex. Proceedings of the National Academy of Sciences of the United States of America 63 23479607
2009 DDB1-CUL4 and MLL1 mediate oncogene-induced p16INK4a activation. Cancer research 63 19208841
2013 Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation. The Journal of biological chemistry 61 23362280
2007 mTORC1 signaling requires proteasomal function and the involvement of CUL4-DDB1 ubiquitin E3 ligase. Cell cycle (Georgetown, Tex.) 60 18235224
2008 VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. Oncogene 58 18332868
2015 The Cullin 4A/B-DDB1-Cereblon E3 Ubiquitin Ligase Complex Mediates the Degradation of CLC-1 Chloride Channels. Scientific reports 56 26021757
2012 Lentivirus Vpr and Vpx accessory proteins usurp the cullin4-DDB1 (DCAF1) E3 ubiquitin ligase. Current opinion in virology 56 23062609
2011 USP1 deubiquitinase maintains phosphorylated CHK1 by limiting its DDB1-dependent degradation. Human molecular genetics 56 21389083
2007 DDB1 is essential for genomic stability in developing epidermis. Proceedings of the National Academy of Sciences of the United States of America 56 17301228
2002 Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2. The Journal of biological chemistry 56 12151405
2009 Ubiquitin ligase components Cullin4 and DDB1 are essential for DNA methylation in Neurospora crassa. The Journal of biological chemistry 55 19948733
2017 Cep78 controls centrosome homeostasis by inhibiting EDD-DYRK2-DDB1VprBP. EMBO reports 48 28242748
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
2010 Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. Genes & development 45 21123655
2013 HIV-1 Vpr protein inhibits telomerase activity via the EDD-DDB1-VPRBP E3 ligase complex. The Journal of biological chemistry 42 23612978
2003 Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities. Journal of virology 42 12743284
2003 Ddb1 is required for the proteolysis of the Schizosaccharomyces pombe replication inhibitor Spd1 during S phase and after DNA damage. The Journal of biological chemistry 42 14701809
2012 CRL4-DDB1-VPRBP ubiquitin ligase mediates the stress triggered proteolysis of Mcm10. Nucleic acids research 41 22570418
2010 Hepatocyte-specific deletion of DDB1 induces liver regeneration and tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 41 21135245
2022 Identification of CUL4A-DDB1-WDFY1 as an E3 ubiquitin ligase complex involved in initiation of lysophagy. Cell reports 40 36103833
2003 Basal transcriptional regulation of human damage-specific DNA-binding protein genes DDB1 and DDB2 by Sp1, E2F, N-myc and NF1 elements. Nucleic acids research 39 12527763
2024 Targeted Protein Degradation through Recruitment of the CUL4 Complex Adaptor Protein DDB1. ACS chemical biology 38 38192078
2015 The CUL4-DDB1 ubiquitin ligase complex controls adult and embryonic stem cell differentiation and homeostasis. eLife 36 26613412
2021 HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver. Theranostics 32 34373747
2002 Characterization of a Schizosaccharomyces pombe strain deleted for a sequence homologue of the human damaged DNA binding 1 (DDB1) gene. The Journal of biological chemistry 32 12181326
2020 Hepatitis B Virus HBx Protein Mediates the Degradation of Host Restriction Factors through the Cullin 4 DDB1 E3 Ubiquitin Ligase Complex. Cells 31 32235678
2018 Algal photoprotection is regulated by the E3 ligase CUL4-DDB1DET1. Nature plants 31 30598533
2008 Cellular concentrations of DDB2 regulate dynamic binding of DDB1 at UV-induced DNA damage. Molecular and cellular biology 31 18936169
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
2020 The Human Cytomegalovirus pUL145 Isoforms Act as Viral DDB1-Cullin-Associated Factors to Instruct Host Protein Degradation to Impede Innate Immunity. Cell reports 29 32075763
2010 The functions of the HIV1 protein Vpr and its action through the DCAF1.DDB1.Cullin4 ubiquitin ligase. Cytokine 29 20347598
2018 Regulation of Smoothened ubiquitylation and cell surface expression through a Cul4-DDB1-Gβ E3 ubiquitin ligase complex. Journal of cell science 28 29930086
2017 DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver. Diabetes 28 28790135
2016 Human DNA Ligase I Interacts with and Is Targeted for Degradation by the DCAF7 Specificity Factor of the Cul4-DDB1 Ubiquitin Ligase Complex. The Journal of biological chemistry 28 27573245
2015 FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex. PloS one 28 25970626
2023 CUL4B-DDB1-COP1-mediated UTX downregulation promotes colorectal cancer progression. Experimental hematology & oncology 27 37679762
2012 The Cul4A-DDB1 E3 ubiquitin ligase complex represses p73 transcriptional activity. Oncogene 27 23085759
2017 NRIP/DCAF6 stabilizes the androgen receptor protein by displacing DDB2 from the CUL4A-DDB1 E3 ligase complex in prostate cancer. Oncotarget 26 28212551
2012 Raf1 Is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification. PLoS genetics 26 22319459
2017 Sirtuin 7-dependent deacetylation of DDB1 regulates the expression of nuclear receptor TR4. Biochemical and biophysical research communications 25 28623141
2000 Studies of the murine DDB1 and DDB2 genes. Gene 25 10713455
2000 Dissociation of DDB1-binding and transactivation properties of the hepatitis B virus X protein. Virus research 25 10930665
2018 Deletion of DDB1- and CUL4- associated factor-17 (Dcaf17) gene causes spermatogenesis defects and male infertility in mice. Scientific reports 24 29907856
2016 DDB1 and CUL4 associated factor 11 (DCAF11) mediates degradation of Stem-loop binding protein at the end of S phase. Cell cycle (Georgetown, Tex.) 23 27254819
2018 HIV-1 Vpr hijacks EDD-DYRK2-DDB1DCAF1 to disrupt centrosome homeostasis. The Journal of biological chemistry 22 29724823
2015 CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activity by Promoting Ubiquitination-Dependent Degradation of the Mammalian CRY1. PloS one 22 26431207
2022 Chlorogenic Acid Activates Nrf2/SKN-1 and Prolongs the Lifespan of Caenorhabditis elegans via the Akt-FOXO3/DAF16a-DDB1 Pathway and Activation of DAF16f. The journals of gerontology. Series A, Biological sciences and medical sciences 21 35279029

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