ArticleRedox biology2021
Selective modulation by PARP-1 of HIF-1α-recruitment to chromatin during hypoxia is required for tumor adaptation to hypoxic conditions.
Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Pamiparib as consolidation treatment after concurrent chemoradiotherapy of limited-stage small cell lung cancer: a single-arm, open-label phase 2 trial.Radiation oncology (London, England) · 2024Trial
- HIF-1α/NREP axis promotes hypertrophic scar fibroblast proliferation and collagen deposition via activation of the TGF-β1/Smad pathway.Biology direct · 2026Article
- PARP inhibitors target cellular energy metabolism: Mechanisms of action and clinical implications.Translational oncology · 2026Review
- Function ofInsects · 2026Article
- HIFU postoperative hypoxia-activated metal-organic frameworks modulate the tumor microenvironment to augment immunotherapy.Journal of nanobiotechnology · 2026Article
- MeCP2 at the crossroads of hypoxia, oxidative stress, and gene regulation in Rett syndrome.Epigenomics · 2025Review
- Article
- Sulfur-Containing Heterocyclic Aromatic Hydrocarbons Alter Estrogen Metabolism and Cause DNA Damage and Apoptosis in Granulosa Cells.International journal of molecular sciences · 2025Article
- Synthetic Lethality-Based Targets and Their Exploration in Tumour Combination Strategies.Journal of cellular and molecular medicine · 2025Review
- HIF1A-mediated pathways promote euploid cell survival in chromosomally mosaic embryos.bioRxiv : the preprint server for biology · 2025Article
- Manganese mitigates atrazine-induced oxidative stress and hepatorenal toxicity: insights from network pharmacology and in vivo experimentation.BMC pharmacology & toxicology · 2025Article
- Post-translational modification of transcription factors: perspectives in vascular medicine.Cell death & disease · 2025Review
- DNA Damage Repair in Glioblastoma: A Novel Approach to Combat Drug Resistance.Cell proliferation · 2025Article
- Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- Emergence of cyclic hypoxia and the impact of PARP inhibitors on tumor progression.NPJ systems biology and applications · 2024Article
- Claudin-4 remodeling of nucleus-cell cycle crosstalk maintains ovarian tumor genome stability and drives resistance to genomic instability-inducing agents.bioRxiv : the preprint server for biology · 2024Article
- Transcriptional regulation mechanism of PARP1 and its application in disease treatment.Epigenetics & chromatin · 2024Review
- Protective and Regenerative Effects of Reconstituted HDL on Human Rotator Cuff Fibroblasts under Hypoxia: An In Vitro Study.Antioxidants (Basel, Switzerland) · 2024Article
- Hypoxia-induced SKA3 promoted cholangiocarcinoma progression and chemoresistance by enhancing fatty acid synthesis via the regulation of PAR-dependent HIF-1a deubiquitylation.Journal of experimental & clinical cancer research : CR · 2023Article
- Nicotinamide Antagonizes Lipopolysaccharide-Induced Hypoxic Cell Signals in Human Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundThe adaptation to hypoxia is mainly controlled by the HIF transcription factors. Increased expression/activity of HIF-1α correlates with poor prognosis in cancer patients. PARP-1 inhibitors are used in the clinic to treat BRCAness breast/ovarian cancer and have been shown to regulate the hypoxic response; therefore, their use could be expanded.
methodsIn this work by integrating molecular/cell biology approaches, genome-wide ChIP-seq, and patient samples, we elucidate the extent to which PARP-1 exerts control over HIF-1-regulated genes.
resultsIn human melanoma, PARP-1 and HIF-1α expression are strongly associated. In response to a hypoxic challenge poly(ADP-ribose) (PAR) is synthesized, HIF-1α is post-transcriptionally modified (PTM) and stabilized by PARylation at specific K/R residues located at its C-terminus. Using an unbiased ChIP-seq approach we demonstrate that PARP-1 dictates hypoxia-dependent HIF-recruitment to chromatin in a range of HIF-regulated genes while analysis of HIF-binding motifs (RCGTG) reveals a restriction on the recognition of hypoxia responsive elements in the absence of PARP-1. Consequently, the cells are poorly adapted to hypoxia, showing a reduced fitness during hypoxic induction.
conclusionsThese data characterize the fine-tuning regulation by PARP-1/PARylation of HIF activation and suggest that PARP inhibitors might have therapeutic potential against cancer types displaying HIF-1α over-activation.
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