Property Summary

NCBI Gene PubMed Count 48
PubMed Score 45.31
PubTator Score 46.41

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (30)

Disease log2 FC p
malignant mesothelioma 1.600 8.6e-07
esophageal adenocarcinoma 1.600 1.8e-02
astrocytoma 1.200 1.9e-07
glioblastoma 3.800 2.9e-11
oligodendroglioma 1.600 3.6e-07
posterior fossa group A ependymoma 2.200 2.0e-05
group 3 medulloblastoma 5.100 7.4e-10
atypical teratoid/rhabdoid tumor 3.600 2.8e-13
medulloblastoma, large-cell 4.800 1.8e-07
primitive neuroectodermal tumor 4.200 2.1e-06
Atopic dermatitis 1.200 2.8e-04
adrenocortical carcinoma 3.432 1.6e-06
non-small cell lung cancer 2.264 4.2e-19
intraductal papillary-mucinous carcinoma... 2.800 2.6e-04
intraductal papillary-mucinous neoplasm ... 3.200 1.8e-03
colon cancer 2.200 4.5e-05
lung cancer 1.100 1.9e-03
pancreatic cancer 1.600 8.8e-05
interstitial cystitis 2.500 1.9e-05
lung adenocarcinoma 1.100 2.6e-07
pediatric high grade glioma 3.500 2.8e-08
nasopharyngeal carcinoma 2.300 3.5e-07
psoriasis 1.500 4.3e-09
Endometriosis 1.871 4.0e-02
Breast cancer 3.200 4.3e-27
breast carcinoma 2.300 1.3e-48
ductal carcinoma in situ 3.400 1.4e-03
invasive ductal carcinoma 3.500 4.6e-04
ovarian cancer 2.300 1.8e-07
pituitary cancer 1.100 1.2e-02

 GWAS Trait (1)

Protein-protein Interaction (5)

Gene RIF (37)

PMID Text
25483090 These findings reveal C/EBPalpha regulates G1/S cell cycle arrest in response to DNA damage via the control of CRL4(Cdt2) mediated degradation of p21.
25483071 CDT2 mediated XPG elimination from DNA damage sites clears the chromatin space needed for repair.
25411249 CDK1 activity blocks CRL4CDT2 by preventing chromatin recruitment of the substrate receptor, CDT2.
25154416 Data shows that phosphorylation of Cdt2 at T464 is important fot its interaction with Cdt2.
25115388 CDT2 likely is a non-oncogene to which transformed cells become addicted because of their enhanced cellular stress, such as replicative stress and DNA damage.
24962565 CRL4(Cdt2)-dependent degradation of TDG occurs in S phase because of the requirement for TDG to interact with chromatin-loaded PCNA, and this degradation is important for preventing toxicity from excess TDG.
24699724 while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers
24022480 ubiquitination of p12 through CRL4(Cdt2) and subsequent degradation form one mechanism by which a cell responds to DNA damage to inhibit fork progression.
23995842 Data indicate that depleting ubiquitin E3 ligase CRL4(CDT2/DCAF2) mimicked the pharmacological effects of MLN4924.
23913683 Data indicate that CRL4(Cdt2) regulates the degradation of the p12 subunit of Pol delta4.
23892434 TGF-beta signaling promotes exit from the cell cycle and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2.
23555860 Non-canonical CRL4A/4B(CDT2) interacts with RAD18 to modulate post replication repair and cell survival.
23478445 Migration of epithelial cells is stimulated by CRL1(FBXO11)-mediated downregulation of Cdt2 and the consequent stabilization of Set8.
23478441 The functional interaction between FBXO11 and CDT2 is evolutionary conserved from worms to humans and plays an important role in regulating the timing of cell-cycle exit.
23109433 CRL4 is a major regulator of CHK1 stability. CRL4CDT2 targets CHK1 for ubiquitination in the nucleoplasm, and for PCNA-independent degradation. CHK1 is required for G2 arrest in CDT2-depleted cells.
23029527 ATR, activated after DNA damage, phosphorylates Cdt2 and promotes the rapid degradation of Cdt1 after UV irradiation in the G1 phase of the cell cycle.
22287560 data identified miR-30a-5p as a tumor-suppressing miRNA in colon cancer cells exerting its function via modulation of DTL expression, which is frequently overexpressed in colorectal cancer
21846465 Studies suggest that DNA damage-induced ubiquitination or sumoylation of PCNA prevents CRL4Cdt2-dependent degradation by inhibiting binding of Cdt1 to PCNA.
21822310 CDT2, a 1q-located candidate gene encoding a protein involved in ubiquitin ligase activity and significantly overexpressed in 1qG Ewing sarcoma, was validated in vitro and in vivo proving its major contribution to this molecular and clinical phenotype
21725088 N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) triggers MSH2 and Cdt2 protein-dependent degradation of the cell cycle and mismatch repair (MMR) inhibitor protein p21Waf1/Cip1.
21550341 Studies indicate the modular architecture of DDB1-CUL4 in complex with DDB2, CSA and CDT2 in DNA repair of UV-induced DNA lesions.
21220508 The turnover of SET8 is accelerated after ultraviolet irradiation dependent on the CRL4(CDT2) ubiquitin ligase and PCNA.
20932472 CRL4(Cdt2)-dependent destruction of Set8 in S phase preserves genome stability by preventing aberrant chromatin compaction during DNA synthesis.
20932471 Results demonstrate a central role of CRL4(Cdt2)-dependent cell-cycle regulation of Set8 for the maintenance of a stable epigenetic state essential for cell viability.
20932471 This study identifies CRL4-Cdt2 ubiquitin ligase to promote the ubiquitin-dependent proteolysis of the histone H4 methyltransferase Set8 during S-phase of the cell cycle and after UV-irradiation in a reaction that is dependent on PCNA.
20929861 Cdt1 degradation following UV irradiation occurs rapidly at damaged sites due to PCNA chromatin loading and the recruitment of Cdt1 and CRL4(Cdt2), before DNA damage repair is completed
20433742 miR-215, through the suppression of DTL expression, induces a decreased cell proliferation leading to an increase in chemoresistance
19672268 RAMP plays an oncogenic role in gastric carcinogenesis
18794347 CDT2/DTL functions as a substrate recognition factor for the Cul4-DDB1-Roc1 E3 ubiquitin ligase to promote PCNA-dependent ubiquitylation and degradation of the CDK inhibitor CDKN1A, both in S-phase of the cell cycle and after UV irradiation.
18703516 CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation
18649358 Observational study of gene-disease association. (HuGE Navigator)
18542055 roles of DTL/RAMP in growth of breast cancer cells and suggest that DTL/RAMP might be a promising molecular target for treatment of breast cancer.
17106265 L2DTL encodes a nuclear protein with centrosome targeting in mitosis, and plays important roles in DNA synthesis, cell cycle progression, cytokinesis, proliferation, and differentiation.
17085480 DTL promotes genomic stability through two distinct mechanisms. First, it is an essential component of the CUL4-DDB1 complex that controls CDT1 levels, thereby preventing rereplication. Second, it is required for the early G2/M checkpoint.
16949367 These studies uncover diverse substrate receptors for Cul4 and identify Cdt2 as a conserved component of the Cul4-Ddb1 E3 that is essential to destroy Cdt1 and ensure proper cell cycle regulation of DNA replication.
16861906 L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage.
16861890 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.

AA Sequence

MLFNSVLRQPQLGVLRNGWSSQYPLQSLLTGYQCSGNDEHTSYGETGVPVPPFGCTFSSAPNMEHVLAVA      1 - 70
NEEGFVRLYNTESQSFRKKCFKEWMAHWNAVFDLAWVPGELKLVTAAGDQTAKFWDVKAGELIGTCKGHQ     71 - 140
CSLKSVAFSKFEKAVFCTGGRDGNIMVWDTRCNKKDGFYRQVNQISGAHNTSDKQTPSKPKKKQNSKGLA    141 - 210
PSVDFQQSVTVVLFQDENTLVSAGAVDGIIKVWDLRKNYTAYRQEPIASKSFLYPGSSTRKLGYSSLILD    211 - 280
STGSTLFANCTDDNIYMFNMTGLKTSPVAIFNGHQNSTFYVKSSLSPDDQFLVSGSSDEAAYIWKVSTPW    281 - 350
QPPTVLLGHSQEVTSVCWCPSDFTKIATCSDDNTLKIWRLNRGLEEKPGGDKLSTVGWASQKKKESRPGL    351 - 420
VTVTSSQSTPAKAPRAKCNPSNSSPSSAACAPSCAGDLPLPSNTPTFSIKTSPAKARSPINRRGSVSSVS    421 - 490
PKPPSSFKMSIRNWVTRTPSSSPPITPPASETKIMSPRKALIPVSQKSSQAEACSESRNRVKRRLDSSCL    491 - 560
ESVKQKCVKSCNCVTELDGQVENLHLDLCCLAGNQEDLSKDSLGPTKSSKIEGAGTSISEPPSPISPYAS    561 - 630
ESCGTLPLPLRPCGEGSEMVGKENSSPENKNWLLAMAAKRKAENPSPRSPSSQTPNSRRQSGKKLPSPVT    631 - 700
ITPSSMRKICTYFHRKSQEDFCGPEHSTEL                                            701 - 730
//

Text Mined References (61)

PMID Year Title
25483090 2014 C/EBP? regulates CRL4(Cdt2)-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint.
25483071 2015 Cdt2-mediated XPG degradation promotes gap-filling DNA synthesis in nucleotide excision repair.
25411249 2015 CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis.
25154416 2014 14-3-3 proteins play a role in the cell cycle by shielding cdt2 from ubiquitin-mediated degradation.
25115388 2014 The stress phenotype makes cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase.
24962565 2014 CRL4Cdt2 E3 ubiquitin ligase and proliferating cell nuclear antigen (PCNA) cooperate to degrade thymine DNA glycosylase in S phase.
24699724 2014 Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction with PCNA.
24022480 2013 Degradation of p12 subunit by CRL4Cdt2 E3 ligase inhibits fork progression after DNA damage.
23995842 2013 Ubiquitin E3 ligase CRL4(CDT2/DCAF2) as a potential chemotherapeutic target for ovarian surface epithelial cancer.
23913683 2013 A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA polymerase ? in response to DNA damage and during the S phase.
23892434 2013 Regulation of TGF-? signaling, exit from the cell cycle, and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2.
23677613 2013 The helicase FBH1 is tightly regulated by PCNA via CRL4(Cdt2)-mediated proteolysis in human cells.
23555860 2013 Non-canonical CRL4A/4B(CDT2) interacts with RAD18 to modulate post replication repair and cell survival.
23478445 2013 CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration.
23478441 2013 Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23109433 2013 CRL4(CDT2) targets CHK1 for PCNA-independent destruction.
23029527 2012 Checkpoint kinase ATR phosphorylates Cdt2, a substrate receptor of CRL4 ubiquitin ligase, and promotes the degradation of Cdt1 following UV irradiation.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22287560 2012 MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL.
22223895 2012 Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-?-acetylation features.
21846465 2011 Ub-family modifications at the replication fork: Regulating PCNA-interacting components.
21822310 2012 1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma.
21725088 2011 N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) triggers MSH2 and Cdt2 protein-dependent degradation of the cell cycle and mismatch repair (MMR) inhibitor protein p21Waf1/Cip1.
21628527 2011 Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ubiquitin-conjugating enzymes via the CRL4Cdt2 ubiquitin ligase complex.
21550341 2011 Detecting UV-lesions in the genome: The modular CRL4 ubiquitin ligase does it best!
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21269460 2011 Initial characterization of the human central proteome.
21220508 2011 SET8 is degraded via PCNA-coupled CRL4(CDT2) ubiquitylation in S phase and after UV irradiation.
20932472 2010 CRL4(Cdt2)-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase.
20932471 2010 CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation.
20929861 2010 Proliferating cell nuclear antigen-dependent rapid recruitment of Cdt1 and CRL4Cdt2 at DNA-damaged sites after UV irradiation in HeLa cells.
20881960 2010 Hundreds of variants clustered in genomic loci and biological pathways affect human height.
20433742 2010 Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells.
20129063 2010 CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19672268 2009 Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19332548 2009 Ionizing radiation induces ATM-independent degradation of p21Cip1 in transformed cells.
18794348 2008 The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing.
18794347 2008 PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex.
18703516 2008 CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18649358 2008 Replication of a genome-wide case-control study of esophageal squamous cell carcinoma.
18542055 2008 Involvement of elevated expression of multiple cell-cycle regulator, DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein), in the growth of breast cancer cells.
17106265 2006 Role of L2DTL, cell cycle-regulated nuclear and centrosome protein, in aggressive hepatocellular carcinoma.
17085480 2006 DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint.
17041588 2006 CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16964240 2006 Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery.
16949367 2006 A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1.
16861906 2006 L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage.
16861890 2006 L2DTL/CDT2 and PCNA interact with p53 and regulate p53 polyubiquitination and protein stability through MDM2 and CUL4A/DDB1 complexes.
16751776 2006 A germline-specific class of small RNAs binds mammalian Piwi proteins.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11278750 2001 Cloning and expression of a novel nuclear matrix-associated protein that is regulated during the retinoic acid-induced neuronal differentiation.