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Lead Time
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Usage
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively. Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1. DDB1-mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-mediated gluconeogenesis in the liver.
Gene References into Functions
These results suggest that different DDB1-CUL4 associated factors play distinct roles in human lung adenocarcinoma development.PMID:28336923
The DDB1 is acetylated and acetylation promotes DDB1 binding to CUL4.PMID:28886238
Results revealed a function independent of its transcriptional activity, as TTF-1 was found to interact with DDB1 and block its binding to CHK1, which in turn attenuated ubiquitylation and subsequent degradation of CHK1.PMID:28192407
SIRT7 inhibits TR4 degradation by deacetylation of DDB1.PMID:28623141
the c-Abl non-receptor kinase phosphorylates DDB1 at residue Tyr-316 to recruit a small regulatory protein, DDA1, leading to increased substrate ubiquitinationPMID:28087699
knockdown of DCAF7 reduced the degradation of DNA ligase I in response to inhibition of proliferation and replacement of ubiquitylated lysine residues reduced the in vitro ubiquitylation of DNA ligase I by Cul4-DDB1 and DCAF7. In contrast, a different E3 ubiquitin ligase regulates FEN-1 turnover.PMID:27573245
This study presents the crystal structure of the DDB1-DCAF1-HIV-1-Vpr-uracil-DNA glycosylase (cyclin U) complex.PMID:27571178
Our data are consistent with the idea that the CUL4A/B-DDB1-CRBN complex catalyses the polyubiquitination and thus controls the degradation of CLC-1 channels.PMID:26021757
These results revealed a novel role of DDB in H3K56Ac deacetylation during early step of NER and the existence of active functional cross-talk between DDB-mediated damage recognition and H3K56Ac deacetylation.PMID:26255936
The identification of Vpr mutants which associate with DCAF1 but only poorly with DDB1 suggests that DCAF1 is necessary but is not sufficient for the Vpr association with DDB1-containing E3 ligase complex.PMID:24912982
Data support a model wherein DDB1 and DDB2 cooperate to repress Bcl-2 transcription. DDB2 recognizes and binds to the Bcl-2 P1 promoter, and HDAC1 is recruited through the DDB1 subunit associated with DDB2 to deacetylate histone H3K9.PMID:24249678
The study presents the crystal structure of human CRBN bound to DDB1 and the drug lenalidomide.PMID:25108355
CUL4A-DDB1-Rbx1 E3 ligase controls the quality of the PTS2 receptor Pex7p.PMID:24989250
structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomidePMID:25043012
In the three intrinsically IMiD-resistant cell lines that clearly express detectable levels of cereblon, the absence of CRBN and DDB1 mutations suggest that potential cereblon-independent mechanisms of resistance existPMID:24166296
UV-DDB examines sites on DNA in discrete steps before forming long-lived, nonmotile UV-DDB dimers (DDB1-DDB2)2 at sites of damage.PMID:24760829
p73 interacts with the CDL4A complex by binding directly to DDB1. The CDL4A complex is able to monoubiquitylate p73, negatively affecting its transcriptional function.PMID:23085759
As a molecular adaptor, Vpr enhanced the interaction between TERT and the VPRBP substrate receptor of the DYRK2-associated EDD-DDB1-VPRBP E3 ligase complex, resulting in increased ubiquitination of TERT.PMID:23612978
Data indicate that Dyrk2 phosphorylates TERT protein, which is then associated with the EDD-DDB1-VprBP E3 ligase complex for subsequent ubiquitin-mediated TERT protein degradation.PMID:23362280
Our findings suggest that DDB1 is a cellular substrate of NS3/4A required for Hepatitis c viurs replication.PMID:23137809
The EZH2-DCAF1/DDB1/CUL4 represents a previously unrecognized methylation-dependent ubiquitination machinery specifically recognizing "methyl degron"; nonhistone protein stability can be dynamically regulated in a methylation-dependent manner.PMID:23063525
potential GRK5 interacting proteins and the association of GRK5 with DDB1 in cell and the regulation of GRK5 level by DDB1-CUL4 ubiquitin ligase complex-dependent proteolysis pathwayPMID:22952844
Findings indicate structural and conformational insights of the DDB1-CUL4A(DDB2) E3 ligase, with significant implications for the regulation and overall organization of the proteins responsible for initiation of nucleotide-excision repair (NER) pathway.PMID:22822215
The data suggested that HomolD-containing promoters require the RNA polymerase II machinery and the proteins DDB1 and RECQL for accurate transcription.PMID:22705827
Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication.PMID:22342275
crystals of CSA-DDB1 had unit-cell parameters a = b = 142.03, c = 250.19 A and diffracted to 2.9 A resolution on beamline ID14-1PMID:22232169
Studies indicate the modular architecture of DDB1-CUL4 in complex with DDB2, CSA and CDT2 in DNA repair of UV-induced DNA lesions.PMID:21550341
damage-specific DNA binding protein 1 is essential to regulation of p27(kip1) turnover after a mild DNA damagePMID:21237244
the CUL4A.DDB1 E3 complex is important for regulation of RASSF1A during mitosis, and it may contribute to inactivation of RASSF1A and promoting cell cycle progressionPMID:21205828
This review focuses on Vpr and its HIV2/SIV counterparts, Vpx and Vpr, which all engage the DDB1.Cullin4 ubiquitin ligase complex through the DCAF1 adaptor protein.PMID:20347598
DDB1 modulates the function of APC/C(Cdh1) in a manner independent of the Cul4-DDB1 complexPMID:20395298
The data suggest that DDB1 could potentially be developed into biomarkers of resistance to acyl sulfonamide-based cancer drugs. This will require clinical validation in a series of patients treated with R3200.PMID:19723642
Studies indicate that CUL4 uses a large beta-propeller protein, DDB1, as a linker to interact with a subset of WD40 proteins.PMID:19818632
Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiationPMID:12034848
findings substantiate the physical and functional connection between the hepatitis B virus X protein and the DDB1-DDB2 heterodimer, leading to the regulation of the pool of the viral proteinPMID:12050362
These findings indicate that hepatitis B virus X protein acts through a pathway that involves a DDB2-independent nuclear function of DDB1 and that this activity will depend on the relative concentration of DDB1 and DDB2 in cells.PMID:12151405
essential for the targeted degradation of STAT1 by the V protein of the paramyxovirus simian virus 5. DDB1 may form a multiprotein complex with STAT1, STAT2, and V for this degradation.PMID:12388698
SV5-V and HBx have evolved to bind DDB1 to achieve distinct functions in their life cycle, both by a mechanism that does not involve DDB2.PMID:12743284
DET1 promotes ubiquitination and degradation of c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1PMID:14739464
Damaged DNA binding protein 1 is a component of the centromere complex in interphase cells.PMID:15009096
results show that HBx in association with DDB1 acts in the nucleus and stimulates hepatitis B virus replication mainly by enhancing viral mRNA levelsPMID:15767425
DDB1-DDB2 protein complex recognizes DNA mismatches and lesionsPMID:16223728
PCNA is involved in mediating Cdt1 degradation by the Cul4-Ddb1 ligase in response to DNA damage.PMID:16407242
Cdt1 degradation requires predominant use of the PCNA/Cul4/Ddb1 ubiquitin ligase pathway after DNA damagePMID:16407252
Monoubiquitinated histone H2A in native chromatin coimmunoprecipitates with the endogenous DDB1-CUL4A(DDB2) complex in response to UV irradiation.PMID:16473935
The F-box protein Skp2, in addition to utilizing Cul1-Skp1, utilizes Cul4A-DDB1 to induce proteolysis of p27Kip1.PMID:16537899
This study uncovers CUL4-DDB-ROC1 as a histone ubiquitin ligase and demonstrate that histone H3 and H4 ubiquitylation participates in the cellular response to DNA damage.PMID:16678110
PCNA, L2DTL and the DDB1-CUL4A complex play critical and differential roles in regulating the protein stability of p53 and MDM2/HDM2 in unstressed and stressed cells.PMID:16861890
L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage.PMID:16861906
Results suggest that DDB1 prevents DNA lesions from accumulating in replicating human cells, in part by regulating Cdt1 degradation.PMID:16940174