ArticleOncogene2021
CRL4A
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Rare protein-coding variation and the genetic architecture of height in >1.4 million individuals.medRxiv : the preprint server for health sciences · 2026Article
- Interactomics of SARS-CoV-2 Macrodomain 1 Reveals Putative Clients of ADP-Ribosyl Hydrolase Activity.Viruses · 2026Article
- Deciphering the Ubiquitin-like Code of DNA-PK: Mechanisms and Therapeutic Opportunities.Biomolecules · 2026Review
- Interactomics of SARS-CoV-2 Macrodomain 1 Reveals Putative Clients of ADP-ribosyl Hydrolase Activity.bioRxiv : the preprint server for biology · 2025Article
- MiR-3202-DTL signaling axis impedes NSCLC malignancy via regulating the ubiquitination-proteasome degradation of p21.Molecular and cellular biochemistry · 2025Article
- Review
- Rewired glycolysis by DTL accelerates oncometabolite L-lactate generation to promote breast cancer progression.Frontiers in oncology · 2025Article
- Hypoxia-induced DTL promotes the proliferation, metastasis, and sorafenib resistance of hepatocellular carcinoma through ubiquitin-mediated degradation of SLTM and subsequent Notch pathway activation.Cell death & disease · 2024Article
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- RUVBL1 ubiquitination by DTL promotes RUVBL1/2-β-catenin-mediated transcriptional regulation of NHEJ pathway and enhances radiation resistance in breast cancer.Cell death & disease · 2024Article
- Osteopontin regulates the growth and invasion of liver cancer cells via DTL.Oncology letters · 2023Article
- FAM60A promotes osteosarcoma development and progression.Cancer medicine · 2023Article
- Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker.BMC cancer · 2023Article
- Targeting the DNA Damage Response Machinery for Lung Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Stress-induced reduction of NaScience advances · 2022Article
- Lentivirus-mediated short hairpin RNA interference of CENPK inhibits growth of colorectal cancer cells with overexpression of Cullin 4A.World journal of gastroenterology · 2022Article
- Bioinformatics Analysis of the Prognostic Significance of CAND1 in ERα-Positive Breast Cancer.Diagnostics (Basel, Switzerland) · 2022Article
- DNA-PKcs participated in hypoxic pulmonary hypertension.Respiratory research · 2022Article
- Multifaceted regulation and functions of 53BP1 in NHEJ‑mediated DSB repair (Review).International journal of molecular medicine · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomic instability induced by DNA damage and improper DNA damage repair is one of the main causes of malignant transformation and tumorigenesis. DNA double strand breaks (DSBs) are the most detrimental form of DNA damage, and nonhomologous end-joining (NHEJ) mechanisms play dominant and priority roles in initiating DSB repair. A well-studied oncogene, the ubiquitin ligase Cullin 4A (CUL4A), is reported to be recruited to DSB sites in genomic DNA, but whether it regulates NHEJ mechanisms of DSB repair is unclear. Here, we discovered that the CUL4A-DTL ligase complex targeted the DNA-PKcs protein in the NHEJ repair pathway for nuclear degradation. Overexpression of either CUL4A or DTL reduced NHEJ repair efficiency and subsequently increased the accumulation of DSBs. Moreover, we demonstrated that overexpression of either CUL4A or DTL in normal cells led to genomic instability and malignant proliferation. Consistent with the in vitro findings, in human precancerous lesions, CUL4A expression gradually increased with increasing malignant tendency and was negatively correlated with DNA-PKcs and positively correlated with γ-H2AX expression. Collectively, this study provided strong evidence that the CUL4A-DTL axis increases genomic instability and enhances the subsequent malignant transformation of normal cells by inhibiting NHEJ repair. These results also suggested that CUL4A may be a prognostic marker of precancerous lesions and a potential therapeutic target in cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.