ArticleScience advances2023
Nimbolide targets RNF114 to induce the trapping of PARP1 and synthetic lethality in
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The trial behind it
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Who cites it
38 citing papers in PubMed, 49 citations in OpenAlex.
- CHD1L maintains genome integrity by facilitating okazaki fragment maturation.Nucleic acids research · 2026Article
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Comprehensive insight into nimbolide response against breast cancer treatment: present evidence, emerging strategy and future direction.Molecular biology reports · 2026Review
- RING finger E3 ubiquitin ligases: novel therapeutic opportunities in melanoma.Cellular & molecular biology letters · 2026Review
- Stabilization of AFF1 by PARylation ensures transcriptional restart after DNA damage.Nature chemical biology · 2026Article
- Aberrant expression of TRIM26 suppresses ferroptosis through regulating GPX4 protein stability in colorectal cancer.Molecular biology reports · 2026Article
- Specificity and recognition of the ADP-ribosyl-ubiquitin modification in the DNA damage response.PLoS biology · 2026Article
- A Large-Scale Method to Measure the Stoichiometries of Protein Poly-ADP-Ribosylation.ACS chemical biology · 2026Article
- STING-ERO1 signaling exacerbates PARylation-mediated parthanatos in sepsis.Cell communication and signaling : CCS · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- PARG regulates the proteasomal degradation of TARG1.Cell reports · 2026Article
- Advances in Phase III Clinical Trials and Future Challenges of Targeted Therapy in Advanced Ovarian Cancer.Cancer management and research · 2026Review
- Targeting pancreatic cancer with natural compounds: molecular mechanisms, preclinical evidence, clinical perspectives, and limitations.Frontiers in pharmacology · 2026Review
- E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.Frontiers in oncology · 2026Review
- ADPr gets a ubiquitin upgrade.Nature chemical biology · 2025Article
- Serine ADPr on histones and PARP1 is a cellular target of ester-linked ubiquitylation.Nature chemical biology · 2025Article
- RNF114, a RING E3 ligase that reads and extends the hybrid ADP-ribose-ubiquitin signal.The EMBO journal · 2025Article
- RNF114 and RNF166 exemplify reader-writer E3 ligases that extend K11 polyubiquitin onto sites of MARUbylation.The EMBO journal · 2025Article
- LncRNA ENST00000532153.1 alleviates podocyte injury by inhibiting PARP1-mediated PARylation of ATF3 in diabetic kidney disease.Cellular and molecular life sciences : CMLS · 2025Article
- TRIM28 drives immune evasion via PARP1 SUMOylation and NADJournal for immunotherapy of cancer · 2025Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies have pointed to PARP1 trapping as a key determinant of the anticancer effects of PARP1 inhibitors (PARPi). We identified RNF114, as a PARylation-dependent, E3 ubiquitin ligase involved in DNA damage response. Upon sensing genotoxicity, RNF114 was recruited, in a PAR-dependent manner, to DNA lesions, where it targeted PARP1 for degradation. The blockade of this pathway interfered with the removal of PARP1 from DNA lesions, leading to profound PARP1 trapping. We showed that a natural product, nimbolide, inhibited the E3 ligase activity of RNF114 and thus caused PARP1 trapping. However, unlike conventional PARPi, nimbolide treatment induced the trapping of both PARP1 and PARylation-dependent DNA repair factors. Nimbolide showed synthetic lethality with
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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.