ArticleOncotarget2014
Minor grove binding ligands disrupt PARP-1 activation pathways.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
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- Anticancer Plant Secondary Metabolites Induce Linker Histone Depletion from Chromatin.Frontiers in bioscience (Landmark edition) · 2024Article
- Targeting NPC1 in Renal Cell Carcinoma.Cancers · 2024Article
- Poly(ADP)-Ribosylation Inhibition: A Promising Approach for Clear Cell Renal Cell Carcinoma Therapy.Cancers · 2021Article
- Histone-dependent PARP-1 inhibitors: A novel therapeutic modality for the treatment of prostate and renal cancers.Urologic oncology · 2021Review
- Novel allosteric PARP1 inhibitors for the treatment of BRCA-deficient leukemia.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2020Article
- Non-NAD-like PARP-1 inhibitors in prostate cancer treatment.Biochemical pharmacology · 2019Article
- Hit and run versus long-term activation of PARP-1 by its different domains fine-tunes nuclear processes.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The multifunctional protein YB-1 potentiates PARP1 activity and decreases the efficiency of PARP1 inhibitors.Oncotarget · 2018Article
- The convergent roles of NF-κB and ER stress in sunitinib-mediated expression of pro-tumorigenic cytokines and refractory phenotype in renal cell carcinoma.Cell death & disease · 2018Article
- LDL cholesterol counteracts the antitumour effect of tyrosine kinase inhibitors against renal cell carcinoma.British journal of cancer · 2017Article
- Non-NAD-Like poly(ADP-Ribose) Polymerase-1 Inhibitors effectively Eliminate Cancer in vivo.EBioMedicine · 2016Article
- Piperlongumine and its analogs down-regulate expression of c-Met in renal cell carcinoma.Cancer biology & therapy · 2015Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
PARP-1 is a nuclear enzyme regulating transcription, chromatin restructuring, and DNA repair. PARP-1 is activated by interaction with NAD+, DNA, and core histones. Each route of PARP-1 activation leads to somewhat different outcomes. PARP-1 interactions with core histones control PARP-1 functions during transcriptional activation in euchromatin. DNA-dependent regulation of PARP-1 determines its localization in heterochromatin and PARP-1-dependent silencing. Here we address the biological significance of DNA-dependent PARP-1 regulation in vitro and in vivo. We report that minor grove binding ligands (MGBLs) specifically target PARP-1 interaction with DNA, and, hence, the DNA-dependent pathway of PARP-1 activation. By obstructing its interaction with DNA molecules, MGBLs block PARP-1 activity in vitro and in vivo, as we demonstrate using Drosophila, as well as human cancer-derived cells. We also demonstrate synergistic inhibition of PARP-1, combining MGBLs with conventional NAD+-dependent inhibitors in human cancer cells. These results suggest that combining different classes of PARP-1 inhibitors can precisely modulate PARP-1 activity in living cells, thus holding promise for new avenues of cancer treatment.
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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.