ArticleScientific reports2017
Chromatin remodeling system p300-HDAC2-Sin3A is involved in Arginine Starvation-Induced HIF-1α Degradation at the ASS1 promoter for ASS1 Derepression.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Cell-Type-Resolved Acetylation Regulator Atlas Defines Immune Endotypes and Druggable Vulnerabilities in Psoriasis.Biomedicines · 2026Article
- Multidimensional regulatory mechanisms and translational potential of epigenetic networks in the rheumatoid arthritis disease course.Frontiers in immunology · 2026Review
- Metabolomics and proteomics reveal blocking argininosuccinate synthetase 1 alleviates colitis in mice.Nature communications · 2025Article
- Bifunctionality and Antitumor Efficacy of ZG-126, a Vitamin D Receptor Agonist/Histone Deacetylase Inhibitor Hybrid Molecule.Journal of medicinal chemistry · 2024Article
- CYLD induces high oxidative stress and DNA damage through class I HDACs to promote radiosensitivity in nasopharyngeal carcinoma.Cell death & disease · 2024Article
- The transcriptional regulator Sin3A balances IL-17A and Foxp3 expression in primary CD4 T cells.EMBO reports · 2023Article
- Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex.Nature communications · 2023Article
- Plateau Adaptation Gene Analyses Reveal Transcriptomic, Proteomic, and Dual Omics Expression in the Lung Tissues of Tibetan and Yorkshire Pigs.Animals : an open access journal from MDPI · 2022Article
- Long noncoding RNA LINC01234 promotes hepatocellular carcinoma progression through orchestrating aspartate metabolic reprogramming.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Molecular mechanisms of bifunctional vitamin D receptor agonist-histone deacetylase inhibitor hybrid molecules in triple-negative breast cancer.Scientific reports · 2022Article
- Epithelial argininosuccinate synthetase is dispensable for intestinal regeneration and tumorigenesis.Cell death & disease · 2021Article
- Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.International journal of molecular sciences · 2021Review
- Arginine Signaling and Cancer Metabolism.Cancers · 2021Review
- FOXC1 Downregulates Nanog Expression by Recruiting HDAC2 to Its Promoter in F9 Cells Treated by Retinoic Acid.International journal of molecular sciences · 2021Article
- Targeting the Proline-Glutamine-Asparagine-Arginine Metabolic Axis in Amino Acid Starvation Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Collaboration Between RSK-EphA2 and Gas6-Axl RTK Signaling in Arginine Starvation Response That Confers Resistance to EGFR Inhibitors.Translational oncology · 2020Article
- Innate and adaptive resistance mechanisms to arginine deprivation therapies in sarcoma and other cancers.Cancer drug resistance (Alhambra, Calif.) · 2019Review
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Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
Abstract
Argininosuccinate synthetase 1 (ASS1) is the key enzyme that controls biosynthesis of arginine (Arg). ASS1 is silenced in many human malignancies therefore, these tumors require extracellular Arg for growth. The Arg-degrading recombinant protein, pegylated arginine deiminase (ADI-PEG20), has been in clinical trials for targeting Arg auxotrophic tumors by Arg starvation therapy. Resistance to Arg starvation is often developed through reactivation of ASS1 expression. We previously demonstrated that ASS1 silencing is controlled by HIF-1α and Arg starvation-reactivated ASS1 is associated with HIF-1α downregulation. However, mechanisms underlying ASS1 repression and HIF-1α turnover are not known. Here, we demonstrate that interplay of p300-HDAC2-Sin3A in the chromatin remodeling system is involved in HIF-1α degradation at the ASS1 promoter. The histone acetyltransferase p300 is normally associated with the ASS1 promoter to maintain acetylated H3K14ac and H3K27ac for ASS1 silencing. Arg starvation induces p300 dissociation, allowing histone HDAC2 and cofactor Sin3A to deacetylate these histones at the ASS1 promoter, thereby facilitating HIF-1α-proteasomal complex, driven by PHD2, to degrade HIF-1α in situ. Arg starvation induces PHD2 and HDAC2 interaction which is sensitive to antioxidants. This is the first report describing epigenetic regulation of chromosomal HIF-1α turnover in gene activation that bears important implication in cancer therapy.
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