Affinage

DDB1

DNA damage-binding protein 1 · UniProt Q16531

Length
1140 aa
Mass
127.0 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDB1 is a multi-domain adaptor protein that nucleates the assembly of CUL4-RBX1 E3 ubiquitin ligase complexes by simultaneously engaging cullin scaffolds and a large repertoire of WD40-repeat substrate receptors (DCAFs), thereby directing ubiquitination of diverse substrates in DNA repair, replication licensing, cell cycle control, chromatin modification, and metabolic signaling. Its three β-propeller domains (BPA, BPB, BPC) form a bipartite architecture: BPC docks onto CUL4A/B, while the BPA–BPB double-propeller fold provides a binding platform for DCAF substrate receptors—including DDB2, CDT2, CRBN, DCAF1/VprBP, and FBW5—through a conserved α-helical motif (H-box/DWD box), enabling each CRL4 complex to target specific substrates such as CDT1 (replication licensing, PCNA-dependent), DDB2 and histone H2A (nucleotide excision repair), CHK1 (checkpoint signaling), CRY1 (gluconeogenesis), and TSC2 (mTOR signaling) (PMID:16413485, PMID:16964240, PMID:17079684, PMID:15448697, PMID:19109893, PMID:18381890). This same H-box interface is exploited by viral proteins—HBx (hepatitis B), SV5-V (paramyxovirus), and HIV-1 Vpr/Vpx via DCAF1—that hijack DDB1-CUL4 to redirect ubiquitination toward host defense factors such as STAT1, UNG2, and SAMHD1, facilitating immune evasion and viral replication (PMID:19966799, PMID:16227264, PMID:27571178, PMID:15767425). Loss of DDB1 in proliferating tissues causes accumulation of cell cycle regulators, DNA re-replication, genomic instability, and p53-dependent apoptosis, underscoring its essential role in coupling substrate proteolysis to genome integrity (PMID:17129780, PMID:16940174).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 High

    Establishing DDB1 as a component of a ubiquitin-ligase-dependent proteolytic pathway: before this, DDB1 was known primarily as a DNA-damage-binding protein, but genetic epistasis in S. pombe showed Ddb1 is required for S-phase proteolysis of ribonucleotide reductase inhibitor Spd1, linking it to ubiquitin-mediated substrate turnover.

    Evidence Genetic deletion and epistasis (spd1Δ × ddb1Δ double mutant) in fission yeast

    PMID:14701809

    Open questions at the time
    • Mechanism by which DDB1 connects to the ubiquitin ligase machinery was unknown
    • Whether this proteolytic function was conserved in mammals was untested
  2. 2004 High

    DDB1 was identified as the direct adaptor bridging CUL4A to the replication licensing factor CDT1, establishing for the first time that DDB1 functions as the substrate-linking subunit in a CUL4A E3 ubiquitin ligase, with CDT1 degradation as a key output for preventing re-replication.

    Evidence Co-IP, in vitro binding, in vitro ubiquitination assay, and siRNA knockdown in human cells

    PMID:15448697

    Open questions at the time
    • The structural basis for DDB1–CUL4A interaction was unresolved
    • How DDB1 engaged different substrates (modularity) was unknown
  3. 2005 High

    Two functional arms of DDB1 were substantiated: its role in UV-damage sensing via DDB2 was refined biochemically, and its exploitation by viral proteins was demonstrated—SV5-V was shown to use DDB1 as an adaptor to ubiquitinate STAT1, while HBx required DDB1 binding for HBV replication, establishing viral hijacking as a general feature.

    Evidence Purified DDB1–DDB2 binding assays for lesion recognition; yeast two-hybrid, Co-IP, and in vitro ubiquitination for SV5-V/DDB1/STAT complex; HBx point mutants and RNAi rescue for HBV

    PMID:15767425 PMID:16223728 PMID:16227264

    Open questions at the time
    • How DDB1 structurally accommodates both cellular and viral binding partners was unknown
    • Whether viral proteins and DDB2 compete for the same DDB1 surface was unresolved
  4. 2006 High

    Crystal structures of DDB1 alone and in complex with CUL4A and SV5-V resolved the three-propeller architecture and revealed the bipartite adaptor mechanism: BPC docks CUL4A while BPA–BPB forms a double-propeller platform for substrate receptors. Simultaneously, the DWD/WDXR motif was identified as the conserved element in WD40-repeat DCAFs for DDB1 binding, and numerous DCAF partners (CDT2, WDR5, EED) were catalogued, establishing DDB1 as a modular hub assembling dozens of distinct CRL4 E3 ligases.

    Evidence X-ray crystallography (DDB1 alone, DDB1–SV5-V, DDB1–CUL4A–ROC1); mutagenesis of WDXR motif across 15 DWD proteins; tandem-affinity purification–mass spectrometry

    PMID:16413485 PMID:16964240 PMID:17041588 PMID:17079684

    Open questions at the time
    • Structures of DDB1 with cellular DCAFs (DDB2, CDT2) were not yet available
    • How individual DCAFs achieve substrate specificity was unresolved
  5. 2006 High

    DDB1 was placed at the center of two major genome-maintenance pathways—NER and replication licensing control. DDB1 was shown to be essential for UV-induced chromatin remodeling (DDB2-dependent translocation, CUL4A recruitment, histone H2A monoubiquitination at damage sites), and for PCNA-dependent CDT1 destruction during S phase, with DDB1 depletion causing re-replication, DSBs, and checkpoint activation suppressible by CDT1 co-depletion.

    Evidence siRNA knockdowns with NER assays, chromatin fractionation, FRAP; CDT1 N-terminal mutagenesis and PCNA-binding studies; epistasis by CDT1 co-depletion

    PMID:16407252 PMID:16473935 PMID:16482215 PMID:16940174 PMID:16951172

    Open questions at the time
    • Structural basis of DDB1–DDB2–DNA interaction was unknown
    • How H2A monoubiquitination facilitates downstream NER steps was unclear
  6. 2007 High

    HIV-1 Vpr was shown to exploit the CRL4 machinery via DCAF1/VprBP, establishing a second viral hijacking paradigm distinct from SV5-V; simultaneously, conditional DDB1 knockouts in mouse brain, lens, and epidermis demonstrated that DDB1 is essential for viability of proliferating progenitor cells, with p53-dependent apoptosis as the major outcome of DDB1 loss.

    Evidence TAP-MS, Co-IP, siRNA, Vpr point mutants for HIV; conditional Cre-lox knockouts with p53 genetic rescue in mouse tissues

    PMID:17129780 PMID:17301228 PMID:17314515 PMID:17609381

    Open questions at the time
    • The specific host substrates targeted by Vpr through DDB1 were not identified
    • Whether DDB1 loss phenotypes reflect failure of one or many CRL4 complexes was unresolved
  7. 2008 High

    Two new dimensions of CRL4-DDB1 function were structurally and biochemically defined: the crystal structure of DDB1–DDB2–DNA showed how DDB2 extrudes UV lesions into a binding pocket and kinks DNA to position the associated CUL4 ligase at damage sites; separately, FBW5 was identified as a DCAF recruiting TSC2 to DDB1-CUL4 for degradation, linking the complex to mTOR pathway regulation.

    Evidence X-ray crystallography of DDB1–DDB2–DNA complex; Co-IP, depletion, and Drosophila genetic rescue for FBW5–TSC2

    PMID:18381890 PMID:19109893

    Open questions at the time
    • How DDB2 degradation after damage recognition remodels NER factor access was not fully resolved
    • Whether TSC2 ubiquitination is a conserved mammalian mechanism was not confirmed in vivo
  8. 2009 High

    The substrate repertoire and regulatory logic of CRL4-DDB1 expanded: CHK1 was identified as a direct ubiquitination substrate of CUL4A-DDB1 linking the complex to checkpoint signaling; REDD1 was identified as a substrate connecting DDB1 to mTOR recovery after hypoxia; the HBx–DDB1 crystal structure revealed the conserved α-helical H-box motif shared by both viral hijackers and cellular DCAFs; and live-cell imaging showed DDB2-dependent dynamic recruitment and release of DDB1 at UV damage sites.

    Evidence Co-IP and in vitro ubiquitination for CHK1; Co-IP plus siRNA for REDD1; X-ray crystallography of DDB1–HBx; FRAP live-cell imaging of DDB1-GFP

    PMID:18936169 PMID:19276361 PMID:19557001 PMID:19966799

    Open questions at the time
    • The specific DCAF mediating CHK1 recognition was not identified
    • Whether DDB1 dynamics at damage sites regulate handoff to downstream NER factors was untested
  9. 2013 Medium

    EZH2-generated methyl degrons were shown to be read by DCAF1's chromo domain, connecting histone methyltransferase output to DDB1-CUL4-mediated ubiquitination; separately, TERT was identified as a DDB1-containing EDD-DDB1-VprBP ligase substrate phosphorylated by DYRK2, linking DDB1 to telomerase regulation.

    Evidence Binding studies with chromo-domain mutagenesis for DCAF1-methyldegron recognition; Co-IP and in vitro kinase/ubiquitination for DYRK2–TERT–DDB1

    PMID:23063525 PMID:23362280

    Open questions at the time
    • Whether methyl-degron recognition is a general mechanism for multiple DCAF1 substrates was not established
    • In vivo physiological relevance of DDB1-dependent TERT degradation for telomere length was not tested
  10. 2014 High

    Crystal structures of DDB1–CRBN bound to thalidomide and its analogs (IMiDs) revealed the structural basis for pharmacological substrate redirection: IMiDs occupy a hydrophobic pocket in CRBN's thalidomide-binding domain and create a neomorphic surface that recruits IKZF1/IKZF3 for ubiquitination while displacing the endogenous substrate MEIS2, establishing the molecular glue paradigm for CRL4-DDB1 ligases.

    Evidence X-ray crystallography of DDB1–CRBN with multiple IMiDs; unbiased substrate screen; site-directed mutagenesis in myeloma models

    PMID:25043012 PMID:25108355

    Open questions at the time
    • Full spectrum of IMiD-induced neosubstrates was not catalogued
    • Structural basis for neosubstrate selectivity (e.g., IKZF1 vs. IKZF3 preference) was unresolved
  11. 2016 High

    The HIV-1 Vpr hijacking mechanism was resolved at atomic detail: the crystal structure of DDB1–DCAF1–Vpr–UNG2 showed Vpr creates a neomorphic binding surface on DCAF1 that recruits UNG2 via molecular mimicry of DNA, completing the mechanistic picture of how lentiviruses redirect CRL4-DDB1 to degrade host restriction factors.

    Evidence X-ray crystallography of the quaternary complex

    PMID:27571178

    Open questions at the time
    • Whether other Vpr-targeted substrates use the same recruitment mechanism was unknown
    • Structural basis for Vpx-mediated SAMHD1 recruitment remained distinct and incompletely resolved
  12. 2017 Medium

    DDB1's own post-translational regulation was revealed: SIRT7 deacetylates DDB1 at K1121, reducing DCAF1 binding and thereby attenuating CUL4B/DDB1/DCAF1 ligase activity; concurrently, hepatocyte-specific Ddb1 deletion demonstrated CRL4-DDB1 promotes gluconeogenesis by degrading cryptochrome CRY1 to stabilize FOXO1.

    Evidence SIRT7 deacetylation assays with K1121R mutagenesis; hepatocyte-specific conditional Ddb1 knockout mice with metabolic phenotyping

    PMID:28623141 PMID:28790135

    Open questions at the time
    • Whether K1121 acetylation globally regulates all DCAF interactions or is DCAF1-specific was not tested
    • Whether CRY1 degradation by CRL4-DDB1 occurs through a specific DCAF was not identified
  13. 2020 High

    A molecular glue compound (HQ461) was shown to promote direct CDK12–DDB1 interaction independent of any DCAF, leading to Cyclin K polyubiquitination and degradation, demonstrating that DDB1's BPA–BPB surface can be pharmacologically co-opted to recruit substrates without a conventional substrate receptor.

    Evidence High-throughput chemical screen, genetic validation (loss/gain-of-function), biochemical reconstitution of direct CDK12–DDB1 binding

    PMID:32804079

    Open questions at the time
    • Structural basis of the CDK12–DDB1 glue interface was not determined
    • Whether other kinase–cyclin pairs can be similarly targeted was unexplored
  14. 2022 Medium

    CRL4-DDB1 was linked to lysophagy through the identification of WDFY1 as a DCAF that directs ubiquitination of LAMP2 on damaged lysosomes, initiating autophagic clearance and expanding DDB1 function to organelle quality control.

    Evidence Proteomic screen with transfection-reagent-coated beads, Co-IP, siRNA knockdown, ubiquitination assays

    PMID:36103833

    Open questions at the time
    • Whether this pathway operates in vivo and in multiple tissues was not shown
    • Additional lysosomal substrates of CRL4-DDB1-WDFY1 were not identified
  15. 2024 Medium

    Cysteine C173 on DDB1 was identified as a druggable site for covalent PROTAC development, enabling targeted degradation of BRD4 and androgen receptor in a DDB1-, proteasome-, and NEDDylation-dependent manner, validating DDB1 as a pharmacologically accessible E3 ligase handle beyond CRBN.

    Evidence Cysteine chemoproteomic screening (activity-based protein profiling), PROTAC degradation assays with inhibitor controls

    PMID:38192078

    Open questions at the time
    • Selectivity profile of C173-targeting PROTACs across the proteome was not established
    • Whether covalent DDB1 modification perturbs endogenous CRL4 ligase functions was not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: how DDB1 coordinates simultaneous engagement of dozens of competing DCAFs in a single cell; the full catalog of endogenous CRL4-DDB1 substrates and their physiological DCAF assignments; and the structural and kinetic mechanisms by which molecular glues and PROTACs achieve substrate selectivity on the DDB1 surface.
  • No quantitative model of DCAF competition for DDB1 exists
  • Many DCAF–substrate pairings lack in vivo validation
  • Structural basis of DCAF-independent substrate recruitment (e.g., CDK12 glue) is unresolved

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 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-69306 DNA Replication 5 R-HSA-73894 DNA Repair 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
CDT2CRBNCUL4ACUL4BDCAF1DCAF7DDB2FBW5
Complex memberships
CRL4-CRBN (CUL4-RBX1-DDB1-CRBN)CRL4A (CUL4A-RBX1-DDB1)CRL4B (CUL4B-RBX1-DDB1)UV-DDB (DDB1-DDB2)

Evidence

Reading pass · 41 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: BPC docks DDB1 to the N-terminus of CUL4A, while BPA-BPB form a rigid double-propeller fold that serves as the binding platform for viral hijackers and cellular substrate receptors (DCAFs). X-ray crystallography of DDB1 alone and in complex with SV5-V protein Cell High 16413485
2006 DDB1 uses its BPC propeller domain to bind CUL4A in a manner analogous to SKP1-CUL1, and uses its BPA-BPB double-propeller fold to recruit WD40-repeat substrate receptors (DCAFs), thereby functioning as a dual-interface adaptor assembling the CUL4A-RBX1-DDB1-DCAF E3 ligase. X-ray crystallography of DDB1-CUL4A-ROC1 machinery; tandem-affinity purification of DDB1/CUL4A complexes followed by mass spectrometry Nature High 16964240
2004 DDB1 associates stoichiometrically with CUL4A in vivo, binds CDT1 directly in vitro, and bridges CDT1 to CUL4A in vivo; silencing DDB1 prevented UV-induced rapid CDT1 degradation and CUL4A-mediated CDT1 ubiquitination in vitro, establishing DDB1 as the adaptor linking CDT1 to the CUL4A ubiquitin ligase. Co-immunoprecipitation, in vitro binding assay, in vitro ubiquitination assay, siRNA knockdown Nature cell biology High 15448697
2006 A conserved 'WDXR' motif (DWD box) in WD40-repeat proteins is required for their direct binding to DDB1, and DDB1 functions as the linker mediating DWD protein association with CUL4A-ROC1 to constitute distinct substrate-specific E3 ligases. Mutational analysis of WDXR motif, co-immunoprecipitation, pull-down assays; 15 DWD proteins tested Genes & development High 17079684
2006 DDB1 interacts with multiple WD40-repeat proteins including WDR5, EED, L2DTL/CDT2, and TLE1-3, using them as substrate-specific adaptors; CUL4A-DDB1 interacts with H3-methylated mononucleosomes and inactivation of CUL4 or DDB1 impairs histone H3K4 and H3K9/K27 methylation. Co-immunoprecipitation, affinity purification, siRNA knockdown, histone peptide binding assays Nature cell biology High 17041588
2006 DCAF2/CDT2 functions as a substrate receptor within the CUL4-DDB1 E3 ligase to destroy replication licensing protein CDT1 in S phase and after DNA damage; in Xenopus, CDT2 is recruited to replication forks via CDT1 and PCNA, where CDT1 ubiquitylation occurs. Xenopus egg extract depletion/rescue, siRNA in human cells, co-immunoprecipitation, re-replication assays Molecular cell High 16949367
2008 Crystal structure of DDB1-DDB2 complex alone and bound to DNA containing 6-4PP or abasic site shows that DDB2's WD40 domain exclusively holds the lesion; a DDB2 hairpin inserts into the minor groove, extrudes the photodimer into a binding pocket, and kinks the duplex ~40°, enabling lesion detection and positioning the associated CUL4 ubiquitin ligase near the damage site. X-ray crystallography of DDB1-DDB2-DNA ternary complexes Cell High 19109893
2014 Crystal structure of DDB1-CRBN bound to thalidomide, lenalidomide, and pomalidomide shows that CRBN is a substrate receptor within CRL4(CRBN) and enantioselectively binds IMiDs; IMiDs redirect the CRL4(CRBN) ligase to ubiquitinate IKZF1/IKZF3 while displacing the endogenous substrate MEIS2. X-ray crystallography, unbiased substrate screen, ubiquitination assays Nature High 25043012
2014 Crystal structure of human CRBN-DDB1 bound to lenalidomide reveals that a hydrophobic pocket in the thalidomide-binding domain (TBD) of CRBN accommodates the glutarimide moiety; site-directed mutagenesis of key drug-binding residues abrogated antiproliferative effects in myeloma models. X-ray crystallography plus site-directed mutagenesis in lentiviral myeloma models Nature structural & molecular biology High 25108355
2009 Crystal structure of DDB1 in complex with hepatitis B virus HBx reveals that HBx binds DDB1 through an alpha-helical motif identical to that used by SV5-V protein and shared by cellular DCAFs, establishing a promiscuous alpha-helical 'H-box' as the common structural element anchoring substrate receptors and viral hijackers to the DDB1 double-propeller fold. X-ray crystallography, structure-based functional mutagenesis Nature structural & molecular biology High 19966799
2006 DDB1 knockdown in human cells impairs repair of UV-induced cyclobutane pyrimidine dimers (CPD) but not 6-4PPs; upon UV irradiation, DDB1 translocates from loosely bound to tightly bound chromatin fraction in a DDB2-dependent manner, and is required for UV-induced DDB2 ubiquitylation and degradation as well as for Cul4A recruitment to damage sites. siRNA knockdown, nuclear fractionation, chromatin immunoprecipitation, local UV damage immunofluorescence, repair assays Cancer research High 16951172
2006 The DDB1-CUL4A(DDB2) ligase complex monoubiquitinates histone H2A at UV-damaged DNA sites; this modification is impaired in XP-E cells with DDB2 mutations, and loss of monoubiquitinated H2A correlates with decreased global genome NER. Co-immunoprecipitation of endogenous complexes from UV-irradiated cells; comparison of XP-E (DDB2-mutant) vs. repair-proficient cells PNAS High 16473935
2005 Purified co-expressed DDB1-DDB2 binds UV-induced 6-4 photoproducts and apurinic sites with high affinity, recognizes cyclobutane pyrimidine dimers with ~6-fold preference over undamaged DNA, and also binds 2–3 bp mismatches, indicating DDB acts as a sensor of DNA conformational changes rather than a specific lesion-recognition protein. In vitro binding assays with highly purified DDB1-DDB2 and reconstituted complexes, affinity measurements Journal of Biological Chemistry High 16223728
2006 Two distinct E3 ubiquitin ligases, SCF-Skp2 and DDB1-CUL4, target human CDT1 for proteolysis through distinct N-terminal signals; DDB1-CUL4 activity requires PCNA binding to CDT1 via the first 10 amino acids for degradation during S phase and after DNA damage. siRNA knockdown of Skp2 and Cul4 singly and in combination, mutational analysis of CDT1 N-terminus, PCNA binding assays EMBO Journal High 16482215
2006 PCNA is required as a cofactor for CUL4/DDB1-dependent CDT1 degradation: overexpression of the PCNA-interacting domain of p21/p57 blocks CDT1 degradation; PCNA and CDT1 co-elute by gel filtration and co-immunoprecipitate; PCNA silencing blocks CDT1 degradation after DNA damage in yeast and mammalian cells. Dominant-negative PCNA-binding domain expression, gel filtration, Co-IP, siRNA in human cells and genetic repression in fission yeast Journal of Biological Chemistry High 16407242 16407252
2007 HIV-1 Vpr binds DDB1 through interaction with the DCAF1/VprBP subunit; recruitment of DCAF1 by Vpr is essential for Vpr-mediated G2 cell cycle arrest; DCAF1 bridges Vpr to DDB1, hijacking the CUL4-DDB1(DCAF1) E3 ubiquitin ligase. Tandem affinity purification, Co-IP, siRNA knockdown, Vpr point mutants Cell Cycle / PNAS / PLoS Pathogens (multiple papers) High 17314515 17360488 17609381 17626091 17630831
2016 Crystal structure of DDB1-DCAF1-HIV-1-Vpr-UNG2 complex reveals how Vpr engages DCAF1 to create a new binding interface for UNG2 recruitment; Vpr uses molecular mimicry of DNA via a variable loop for specific UNG2 substrate recruitment, distinct from the SAMHD1 recruitment mechanism of Vpx. X-ray crystallography of quaternary complex Nature structural & molecular biology High 27571178
2005 HBx requires its interaction with DDB1 for both stimulation of HBV genome replication and cell death; DDB1-binding-deficient HBx point mutants fail to complement HBx-deficient HBV; DDB1 depletion by RNAi specifically compromises HBV replication; HBx with DDB1 acts in the nucleus to increase viral mRNA levels. HBx point mutants, DDB1-HBx fusion protein rescue, RNA interference, nuclear/cytoplasmic fractionation Journal of Virology High 15767425
2006 Conditional deletion of DDB1 in mouse brain and lens leads to aberrant accumulation of cell cycle regulators, genomic instability, and p53-dependent apoptosis selectively in proliferating neuronal progenitor cells; partial rescue by p53 deletion places DDB1 upstream of p53 in maintaining viability of dividing cells. Conditional knockout mice (Cre-lox), genetic epistasis with p53 deletion, apoptosis and cell cycle assays Cell High 17129780
2007 Conditional deletion of DDB1 in mouse epidermis causes accumulation of c-Jun and p21Cip1, G2/M arrest, selective apoptosis of proliferating progenitor cells, and loss of epidermis and hair follicles; p53 deletion partially rescues these phenotypes. Tissue-specific conditional knockout (Cre-lox), genetic epistasis with p53 PNAS High 17301228
2006 DDB1-depleted human cells accumulate DNA double-strand breaks and activate ATM/ATR checkpoints; Cdt1 accumulates and causes re-replication in DDB1-depleted cells; these phenotypes are partially suppressed by co-depletion of Cdt1, establishing Cdt1 as a key DDB1 substrate for genome maintenance. siRNA knockdown of DDB1, Cul4A, DDB2, XPA, XPC; epistasis by Cdt1 co-depletion; DNA damage and checkpoint markers Molecular and Cellular Biology High 16940174
2009 DDB1 is identified as a novel CHK1-interacting protein; CUL4A/DDB1 negatively regulates CHK1 stability, directly ubiquitinates CHK1 in vitro, and enhanced interaction occurs upon CHK1 phosphorylation or replication stress; CHK1 is stabilized in CUL4A/DDB1-deficient cells. Co-IP, in vitro ubiquitination assay, siRNA knockdown of CUL4A/DDB1, western blot for CHK1 levels Cancer Research High 19276361
2008 FBW5, a DDB1-binding WD40 protein, recruits TSC2 to the DDB1-CUL4-ROC1 E3 ubiquitin ligase; overexpression of FBW5 or CUL4A promotes TSC2 degradation, prevented by TSC1 co-expression; FBW5/DDB1/CUL4A/B depletion stabilizes TSC2; Drosophila Ddb1/Cul4 mutations cause TSC2 accumulation and growth defects partially rescued by TSC2 reduction. Co-IP, overexpression/depletion experiments, Drosophila genetic rescue Genes & development High 18381890
2013 EZH2 methyltransferase generates monomethylated substrates (methyl degrons) that are directly recognized by the putative chromo domain of DCAF1; DCAF1 bridges monomethylated substrates (e.g., RORα) to DDB1-CUL4 for ubiquitination, establishing methylation-dependent ubiquitination by the DCAF1/DDB1/CUL4 complex. Molecular modeling, binding affinity studies, DCAF1 chromo-domain mutagenesis, Co-IP, ubiquitination assays Molecular cell High 23063525
2011 USP1 deubiquitinase maintains total and phosphorylated CHK1 levels by limiting DDB1-dependent degradation of phosphorylated CHK1; USP1 depletion stimulates DDB1-dependent degradation of phospho-CHK1 in both FANCD2-dependent and -independent manners. siRNA depletion of USP1 and DDB1, western blot analysis of CHK1 levels, epistasis Human Molecular Genetics Medium 21389083
2009 CUL4A-DDB1-ROC1-β-TRCP E3 ligase complex ubiquitinates REDD1 for proteasomal degradation in a GSK3β-dependent manner; REDD1 degradation by CUL4A-DDB1 is required for restoration of mTOR signaling as cells recover from hypoxic stress. Co-IP, siRNA knockdown, ubiquitination assays, mTOR activity measurements EMBO Reports Medium 19557001
2009 DDB1 accumulates rapidly at UV damage sites and dissociates dynamically; DDB2 is indispensable for DDB1 binding to DNA damage sites (CUL4A is not); UV-dependent DDB2 degradation releases DDB1 from damage-associated chromatin, making it available for other functions. Live-cell fluorescence microscopy (FRAP/photobleaching) of fluorescently tagged DDB1; siRNA knockdown of DDB2 and CUL4A Molecular and Cellular Biology High 18936169
2005 In simian virus 5, V protein acts as an adaptor linking DDB1 to STAT2/STAT1 heterodimers; V protein binds DDB1 and STAT2 independently, V protein cannot bind STAT1 directly, and the combined complex STAT1-STAT2-DDB1-V plus accessory factors including CUL4A is sufficient to ubiquitinate STAT1. Yeast two-hybrid, direct protein interaction visualization, Co-IP, in vitro ubiquitination Journal of Virology High 16227264
2012 DDB1-CUL4A complex monoubiquitylates p73 through direct DDB1-p73 interaction; this modification does not affect p73 stability but negatively regulates p73-dependent transcriptional activity, demonstrating a non-proteolytic ubiquitination function of the CUL4A-DDB1 E3. Co-IP, siRNA/genetic depletion of DDB1, transcriptional reporter assays, ubiquitination assays Oncogene Medium 23085759
2013 UCH-L1 disrupts a complex between DDB1-CUL4 and raptor and counteracts DDB1-CUL4-mediated raptor ubiquitination, leading to mTORC1 dissolution and secondary increase in mTORC2. Co-IP, ubiquitination assays, mTOR complex assembly analysis, Uchl1 knockout and transgenic mouse models Molecular and Cellular Biology Medium 23297343
2020 Molecular glue HQ461 promotes direct interaction between CDK12 and DDB1-CUL4-RBX1 E3 ubiquitin ligase, bypassing requirement for a substrate receptor (DCAF), leading to polyubiquitination and degradation of CDK12-associated Cyclin K; biochemical reconstitution confirmed direct CDK12-DDB1 interaction. High-throughput screening, genetic (loss-of-function/gain-of-function screens), biochemical reconstitution, ubiquitination assays, structure-activity relationship analysis eLife High 32804079
2017 DDB1 is deacetylated at Lys1121 by SIRT7; the deacetylation-mimicking K1121R-DDB1 mutant shows reduced binding to DCAF1, attenuating the CUL4B/DDB1/DCAF1 E3 ubiquitin ligase activity and increasing TR4 protein levels; thus SIRT7-mediated deacetylation of DDB1 at K1121 inhibits DCAF1 recruitment. SIRT7 binding and deacetylation assays, mutational analysis (K1121R), Co-IP, TR4 protein level measurements Biochemical and Biophysical Research Communications Medium 28623141
2017 DDB1-CUL4A E3 ligase promotes hepatic gluconeogenesis by degrading CRY1, thereby stabilizing FOXO1; hepatocyte-specific Ddb1 deletion impairs gluconeogenesis, decreases FOXO1 protein, and protects against high-fat diet-induced hyperglycemia. Hepatocyte-specific conditional Ddb1 knockout mice, CRY1 degradation assays, FOXO1 protein levels, gluconeogenesis measurements Diabetes Medium 28790135
2021 CUL4A-DDB1 E3 ligase monoubiquitinates PHGDH at Lys146, enhancing PHGDH activity by recruiting chaperone DNAJA1 to promote its tetrameric formation, thereby increasing serine/glycine/SAM levels and promoting CRC metastasis. Mass spectrometry mapping of ubiquitination site, Co-IP, enzymatic activity assays, chaperone interaction studies Journal of Clinical Investigation Medium 34720086
2022 CUL4A-DDB1-WDFY1 E3 ubiquitin ligase complex is essential for initiation of lysophagy; WDFY1 serves as a DCAF substrate receptor, and the complex ubiquitinates LAMP2 on damaged lysosomes to recruit autophagic machinery. Proteomic screen using transfection reagent-coated beads, Co-IP, siRNA knockdown, ubiquitination assays Cell Reports Medium 36103833
2024 Covalent chemoproteomic screening identified C173 on DDB1 as a targetable cysteine; a covalent DDB1 recruiter was used to develop PROTACs that degrade BRD4 (short isoform selectively) and androgen receptor in a proteasome-, NEDDylation-, and DDB1-dependent manner, demonstrating DDB1 (as CUL4 adaptor) can be targeted for PROTAC applications. Activity-based protein profiling, cysteine chemoproteomic screening, PROTAC degradation assays, proteasome/NEDDylation inhibitors, siRNA knockdown ACS Chemical Biology Medium 38192078
2003 In S. pombe, Ddb1 is required for proteolysis of the ribonucleotide reductase inhibitor Spd1 in S phase and after DNA damage; deletion of spd1 suppresses growth defects and DNA damage sensitivity of Δddb1 cells, placing Ddb1 upstream of Spd1 in RNR regulation. Genetic deletion, epistasis analysis (spd1 Δ×ddb1Δ double mutant), immunoblotting for Spd1 Journal of Biological Chemistry High 14701809
2009 In C. elegans, WDR-23 interacts with CUL-4/DDB-1 ubiquitin ligase to repress SKN-1 protein levels, nuclear accumulation, and transcriptional activity; WDR-23 acts downstream of p38 MAPK, GSK-3, and insulin signaling to regulate SKN-1, suggesting phosphorylation modifies SKN-1 interaction with WDR-23/CUL-4/DDB-1. Genome-wide screen in C. elegans, Co-IP, genetic epistasis with kinase pathway mutations Molecular and Cellular Biology Medium 19273594
2013 Dyrk2 phosphorylates TERT, and phosphorylated TERT is recognized by the EDD-DDB1-VprBP E3 ligase complex for ubiquitin-mediated degradation; DDB1 is a structural component of this complex; Dyrk2 depletion stabilizes TERT and deregulates cell-cycle-dependent telomerase regulation. Co-IP, in vitro kinase assay, ubiquitination assay, siRNA knockdown Journal of Biological Chemistry Medium 23362280
2017 In Drosophila, Cul4-DDB1 E3 ubiquitin ligase promotes ubiquitylation and cell surface clearance of Smoothened (Smo); the Smo C-terminal domain recruits Cul4-DDB1 through trimeric Gβ subunit; Hedgehog signaling disrupts this interaction by triggering PKA-mediated phosphorylation of DDB1, which blocks its binding to Gβ. Drosophila genetics, Co-IP, ubiquitination assays, Smo internalization/trafficking assays Journal of Cell Science Medium 29930086
2016 Human DNA ligase I interacts with and is targeted for degradation by DCAF7, a specificity factor for the CUL4-DDB1 complex; three ubiquitylated lysine residues on DNA ligase I were mapped by mass spectrometry; replacement of these lysines reduced in vitro ubiquitylation by CUL4-DDB1-DCAF7. Proteomic ubiquitylation site mapping, siRNA knockdown of DCAF7, in vitro ubiquitylation assay, lysine mutagenesis Journal of Biological Chemistry Medium 27573245

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 850 25043012
2006 Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature 581 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 536 16949367
2014 Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nature structural & molecular biology 415 25108355
2007 DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Molecular cell 392 17588513
2006 CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nature cell biology 369 17041588
2008 Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex. Cell 349 19109893
2006 Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. The EMBO journal 327 16482215
2004 Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nature cell biology 314 15448697
2006 DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes & development 285 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 217 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 205 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 203 17609381
2009 A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery. Nature structural & molecular biology 181 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
2007 HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase. PLoS pathogens 166 17630831
2020 Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation. eLife 165 32804079
2008 Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction. PLoS pathogens 159 18451984
2004 Arabidopsis COP10 forms a complex with DDB1 and DET1 in vivo and enhances the activity of ubiquitin conjugating enzymes. Genes & development 159 15342494
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
2004 Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase. Genes to cells : devoted to molecular & cellular mechanisms 151 15009096
2011 MSI4/FVE interacts with CUL4-DDB1 and a PRC2-like complex to control epigenetic regulation of flowering time in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 142 21282611
2008 WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase. Genes & development 141 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
2014 ABD1 is an Arabidopsis DCAF substrate receptor for CUL4-DDB1-based E3 ligases that acts as a negative regulator of abscisic acid signaling. The Plant cell 136 24563203
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 133 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
2008 Arabidopsis DDB1-CUL4 ASSOCIATED FACTOR1 forms a nuclear E3 ubiquitin ligase with DDB1 and CUL4 that is involved in multiple plant developmental processes. The Plant cell 123 18552200
2009 REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A-DDB1 ubiquitin ligase. EMBO reports 120 19557001
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 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
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
2006 CUL4 associates with DDB1 and DET1 and its downregulation affects diverse aspects of development in Arabidopsis thaliana. The Plant journal : for cell and molecular biology 105 16792691
2007 Stealing the spotlight: CUL4-DDB1 ubiquitin ligase docks WD40-repeat proteins to destroy. Cell division 104 17280619
2018 Inhibition of HBV Transcription From cccDNA With Nitazoxanide by Targeting the HBx-DDB1 Interaction. Cellular and molecular gastroenterology and hepatology 100 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 98 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
2006 Cul4A and DDB1 associate with Skp2 to target p27Kip1 for proteolysis involving the COP9 signalosome. Molecular and cellular biology 94 16537899
2011 The Cul4-Ddb1(Cdt)² ubiquitin ligase inhibits invasion of a boundary-associated antisilencing factor into heterochromatin. Cell 89 21215368
2021 Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine. The Journal of clinical investigation 86 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
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
2006 DNA damage binding protein component DDB1 participates in nucleotide excision repair through DDB2 DNA-binding and cullin 4A ubiquitin ligase activity. Cancer research 82 16951172
2016 The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction. Nature structural & molecular biology 81 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
2011 The Arabidopsis CUL4-DDB1 complex interacts with MSI1 and is required to maintain MEDEA parental imprinting. The EMBO journal 63 21240189
2009 DDB1-CUL4 and MLL1 mediate oncogene-induced p16INK4a activation. Cancer research 63 19208841
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 62 23479607
2015 Ubiquitin-conjugated degradation of golden 2-like transcription factor is mediated by CUL4-DDB1-based E3 ligase complex in tomato. The New phytologist 61 26352615
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
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
2015 The Cullin 4A/B-DDB1-Cereblon E3 Ubiquitin Ligase Complex Mediates the Degradation of CLC-1 Chloride Channels. Scientific reports 55 26021757
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
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
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
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
2001 DDB2 induces nuclear accumulation of the hepatitis B virus X protein independently of binding to DDB1. Journal of virology 38 11581406
2024 Targeted Protein Degradation through Recruitment of the CUL4 Complex Adaptor Protein DDB1. ACS chemical biology 36 38192078
2022 Identification of CUL4A-DDB1-WDFY1 as an E3 ubiquitin ligase complex involved in initiation of lysophagy. Cell reports 36 36103833
2015 The CUL4-DDB1 ubiquitin ligase complex controls adult and embryonic stem cell differentiation and homeostasis. eLife 36 26613412
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
2021 HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver. Theranostics 31 34373747
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 27 28790135
2015 FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex. PloS one 27 25970626
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
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 26 27573245
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
2023 CUL4B-DDB1-COP1-mediated UTX downregulation promotes colorectal cancer progression. Experimental hematology & oncology 25 37679762
2017 Sirtuin 7-dependent deacetylation of DDB1 regulates the expression of nuclear receptor TR4. Biochemical and biophysical research communications 25 28623141