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    DTL denticleless E3 ubiquitin protein ligase homolog [ Homo sapiens (human) ]

    Gene ID: 51514, updated on 2-Nov-2024

    GeneRIFs: Gene References Into Functions

    GeneRIFPubMed TitleDate
    Circ-DTL sponges miR-758-3p to accelerate cervical cancer malignant progression by regulating DCUN1D1 expression.

    Circ-DTL sponges miR-758-3p to accelerate cervical cancer malignant progression by regulating DCUN1D1 expression.
    Luo X, Liu J, Wang X, Yuan J, Zhang Y.

    03/21/2024
    Epithelial CRL4[DCAF2] Is Critical for Maintaining Intestinal Homeostasis Against DSS-Induced Colitis by Regulating the Proliferation and Repair of Intestinal Epithelial Cells.

    Epithelial CRL4(DCAF2) Is Critical for Maintaining Intestinal Homeostasis Against DSS-Induced Colitis by Regulating the Proliferation and Repair of Intestinal Epithelial Cells.
    Zhang Y, Wang C, Wu L, Bai C, Huang K, Yao L, Zhang Z, Ye L, Liu R, Ge X, Xu M, Zhao Y, Cao Q.

    01/17/2024
    Regular or DCAF2: How CRL4[DCAF2] Affects IBD-Related Mucosal Injury.

    Regular or DCAF2: How CRL4(DCAF2) Affects IBD-Related Mucosal Injury.
    Palla AH.

    01/17/2024
    DTL is a Novel Downstream Gene of E2F1 that Promotes the Progression of Hepatocellular Carcinoma.

    DTL is a Novel Downstream Gene of E2F1 that Promotes the Progression of Hepatocellular Carcinoma.
    Dong R, Zhang D, Han B, Xu L, Zhang D, Cheng Z, Qiu X.

    08/30/2023
    miR-34a negatively regulates cell cycle factor Cdt2/DTL in HPV infected cervical cancer cells.

    miR-34a negatively regulates cell cycle factor Cdt2/DTL in HPV infected cervical cancer cells.
    Singh G, Sharma SK, Singh SK., Free PMC Article

    07/30/2022
    Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment.

    Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment.
    Li Z, Wang R, Qiu C, Cao C, Zhang J, Ge J, Shi Y., Free PMC Article

    04/23/2022
    DTL Is a Prognostic Biomarker and Promotes Bladder Cancer Progression through Regulating the AKT/mTOR axis.

    DTL Is a Prognostic Biomarker and Promotes Bladder Cancer Progression through Regulating the AKT/mTOR axis.
    Luo Y, He Z, Liu W, Zhou F, Liu T, Wang G., Free PMC Article

    03/12/2022
    Overexpression of DTL enhances cell motility and promotes tumor metastasis in cervical adenocarcinoma by inducing RAC1-JNK-FOXO1 axis.

    Overexpression of DTL enhances cell motility and promotes tumor metastasis in cervical adenocarcinoma by inducing RAC1-JNK-FOXO1 axis.
    Liu S, Gu L, Wu N, Song J, Yan J, Yang S, Feng Y, Wang Z, Wang L, Zhang Y, Jin Y., Free PMC Article

    02/5/2022
    CRL4A(DTL) degrades DNA-PKcs to modulate NHEJ repair and induce genomic instability and subsequent malignant transformation.

    CRL4A(DTL) degrades DNA-PKcs to modulate NHEJ repair and induce genomic instability and subsequent malignant transformation.
    Feng M, Wang Y, Bi L, Zhang P, Wang H, Zhao Z, Mao JH, Wei G., Free PMC Article

    10/16/2021
    The rs11275300:G allele in the 3'UTR of DTL may lead to a poor prognosis and allele-specific increase in the expression of DTL by post-transcriptional regulation in acral melanoma.

    Identification of a functional polymorphism within the 3'-untranslated region of denticleless E3 ubiquitin protein ligase homolog associated with survival in acral melanoma.
    Yang L, Dai J, Ma M, Mao L, Si L, Cui C, Sheng X, Chi Z, Yu S, Xu T, Yu J, Kong Y, Guo J.

    06/13/2020
    Our results elucidated that DTL enhanced the motility and proliferation of cancer cells through degrading PDCD4 to promote the development of cancers.

    DTL promotes cancer progression by PDCD4 ubiquitin-dependent degradation.
    Cui H, Wang Q, Lei Z, Feng M, Zhao Z, Wang Y, Wei G., Free PMC Article

    01/18/2020
    As the ligase activity of CRL4Cdt2 depends on proliferating cell nuclear antigen (PCNA) loading onto DNA, the present results suggest that the DNA-binding domain facilitates the CRL4Cdt2-mediated recognition and ubiquitination of substrates bound to PCNA on chromatin.

    A DNA-binding domain in the C-terminal region of Cdt2 enhances the DNA synthesis-coupled CRL4Cdt2 ubiquitin ligase activity for Cdt1.
    Mazian MA, Suenaga N, Ishii T, Hayashi A, Shiomi Y, Nishitani H.

    08/3/2019
    CDT2 has a PIP box-like motif at its C terminus. This motif directly interacts with PCNA to help promote degradation of CDT1 during replication or in response to DNA damage.

    Proliferating cell nuclear antigen interacts with the CRL4 ubiquitin ligase subunit CDT2 in DNA synthesis-induced degradation of CDT1.
    Leng F, Saxena L, Hoang N, Zhang C, Lee L, Li W, Gong X, Lu F, Sun H, Zhang H., Free PMC Article

    04/20/2019
    Results suggest that CDK-mediated phosphorylation of Cdt2 inactivates its ubiquitin ligase activity by reducing its affinity to PCNA, an important strategy for regulating the levels of key proteins in the cell cycle.

    Mutations at multiple CDK phosphorylation consensus sites on Cdt2 increase the affinity of CRL4(Cdt2) for PCNA and its ubiquitination activity in S phase.
    Nukina K, Hayashi A, Shiomi Y, Sugasawa K, Ohtsubo M, Nishitani H.

    09/29/2018
    Findings suggest that DTL overexpression plays a crucial role in tumor cell proliferation in gastric carcinoma.

    Overexpression of denticleless E3 ubiquitin protein ligase homolog (DTL) is related to poor outcome in gastric carcinoma.
    Kobayashi H, Komatsu S, Ichikawa D, Kawaguchi T, Hirajima S, Miyamae M, Okajima W, Ohashi T, Kosuga T, Konishi H, Shiozaki A, Fujiwara H, Okamoto K, Tsuda H, Otsuji E., Free PMC Article

    03/4/2017
    CDT2 mediated XPG elimination from DNA damage sites clears the chromatin space needed for repair.

    Cdt2-mediated XPG degradation promotes gap-filling DNA synthesis in nucleotide excision repair.
    Han C, Wani G, Zhao R, Qian J, Sharma N, He J, Zhu Q, Wang QE, Wani AA., Free PMC Article

    01/2/2016
    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.

    The stress phenotype makes cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase.
    Olivero M, Dettori D, Arena S, Zecchin D, Lantelme E, Di Renzo MF., Free PMC Article

    11/21/2015
    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.

    C/EBPα regulates CRL4(Cdt2)-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint.
    Hall JR, Bereman MS, Nepomuceno AI, Thompson EA, Muddiman DC, Smart RC., Free PMC Article

    09/26/2015
    CDK1 activity blocks CRL4CDT2 by preventing chromatin recruitment of the substrate receptor, CDT2.

    CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis.
    Rizzardi LF, Coleman KE, Varma D, Matson JP, Oh S, Cook JG., Free PMC Article

    04/11/2015
    while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers

    Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction with PCNA.
    Adeyemi RO, Fuller MS, Pintel DJ., Free PMC Article

    12/20/2014
    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.

    CRL4Cdt2 E3 ubiquitin ligase and proliferating cell nuclear antigen (PCNA) cooperate to degrade thymine DNA glycosylase in S phase.
    Shibata E, Dar A, Dutta A., Free PMC Article

    12/20/2014
    Data shows that phosphorylation of Cdt2 at T464 is important fot its interaction with Cdt2.

    14-3-3 proteins play a role in the cell cycle by shielding cdt2 from ubiquitin-mediated degradation.
    Dar A, Wu D, Lee N, Shibata E, Dutta A., Free PMC Article

    11/29/2014
    TGF-beta signaling promotes exit from the cell cycle and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2.

    Regulation of TGF-β signaling, exit from the cell cycle, and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2.
    Abbas T, Keaton M, Dutta A., Free PMC Article

    03/8/2014
    ubiquitination of p12 through CRL4(Cdt2) and subsequent degradation form one mechanism by which a cell responds to DNA damage to inhibit fork progression.

    Degradation of p12 subunit by CRL4Cdt2 E3 ligase inhibits fork progression after DNA damage.
    Terai K, Shibata E, Abbas T, Dutta A., Free PMC Article

    01/4/2014
    Data indicate that depleting ubiquitin E3 ligase CRL4(CDT2/DCAF2) mimicked the pharmacological effects of MLN4924.

    Ubiquitin E3 ligase CRL4(CDT2/DCAF2) as a potential chemotherapeutic target for ovarian surface epithelial cancer.
    Pan WW, Zhou JJ, Yu C, Xu Y, Guo LJ, Zhang HY, Zhou D, Song FZ, Fan HY., Free PMC Article

    12/14/2013
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