ArticleNucleic acids research2022
LncRNA CTBP1-DT-encoded microprotein DDUP sustains DNA damage response signalling to trigger dual DNA repair mechanisms.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Functions of exosome-derived noncoding RNA-encoded polypeptides/proteins in human diseases.Genes & diseases · 2027Review
- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- The long non-coding RNA-encoded microprotein MKKS3 drives colorectal cancer chemoresistance.Experimental & molecular medicine · 2026Article
- The identity crisis of cryptic lncRNAs: when non-coding RNAs translate into small peptides.The EMBO journal · 2026Review
- LncRNA H19-Encoded Micropeptide altH19 Promotes DNA Replication and Mitosis in Myeloma Cells by Enhancing the Phosphorylation of CDK2 at Threonine 160.Cell proliferation · 2026Article
- Revisiting noncoding RNAs: emerging coding functions and their impact on skeletal muscle development.Experimental & molecular medicine · 2026Review
- NAD(H)-dependent corepressor CTBP1 integrates metabolic signals to drive oncogenic programs.Frontiers in immunology · 2026Review
- Long non-coding RNA LOC101926915-encoded micropeptide carboplatin-induced upregulation factor confers carboplatin resistance in ovarian cancer.CytoJournal · 2026Article
- LncRNAs: key regulators and molecular mechanisms in lung cancer radiosensitivity.Open medicine (Warsaw, Poland) · 2026Review
- Micropeptides in the oncological dark matter: decoding their roles in tumor progression and therapy resistance.Journal of translational medicine · 2025Review
- Towards Post-Genomic Oncology: Embracing Cancer Complexity via Artificial Intelligence, Multi-Targeted Therapeutics, Drug Repurposing, and Innovative Study Designs.International journal of molecular sciences · 2025Review
- LncRNA-Encoded Micropeptides: Expression Validation, Translational Mechanisms, and Roles in Cellular Metabolism.International journal of molecular sciences · 2025Review
- Eukaryotic Microproteins.Annual review of biochemistry · 2025Review
- Beyond the Transcript: Translating Non-Coding RNAs and Their Impact on Cellular Regulation.Cancers · 2025Review
- Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance.Molecular cancer · 2025Review
- A large-scale sORF screen identifies putative microproteins involved in cancer cell fitness.iScience · 2025Article
- Long non-coding RNA-encoded micropeptides: functions, mechanisms and implications.Cell death discovery · 2024Review
- Long noncoding RNA AK144717 exacerbates pathological cardiac hypertrophy through modulating the cellular distribution of HMGB1 and subsequent DNA damage response.Cellular and molecular life sciences : CMLS · 2024Article
- CircRNA and lncRNA-encoded peptide in diseases, an update review.Molecular cancer · 2024Review
- LncRNA-encoded peptides in cancer.Journal of hematology & oncology · 2024Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sustaining DNA damage response (DDR) signalling via retention of DDR factors at damaged sites is important for transmitting damage-sensing and repair signals. Herein, we found that DNA damage provoked the association of ribosomes with IRES region in lncRNA CTBP1-DT, which overcame the negative effect of upstream open reading frames (uORFs), and elicited the novel microprotein DNA damage-upregulated protein (DDUP) translation via a cap-independent translation mechanism. Activated ATR kinase-mediated phosphorylation of DDUP induced a drastic 'dense-to-loose' conformational change, which sustained the RAD18/RAD51C and RAD18/PCNA complex at damaged sites and initiated RAD51C-mediated homologous recombination and PCNA-mediated post-replication repair mechanisms. Importantly, treatment with ATR inhibitor abolished the effect of DDUP on chromatin retention of RAD51C and PCNA, thereby leading to hypersensitivity of cancer cells to DNA-damaging chemotherapeutics. Taken together, our results uncover a plausible mechanism underlying the DDR sustaining and might represent an attractive therapeutic strategy in improvement of DNA damage-based anticancer therapies.
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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.