ArticleRedox biology2020
Peroxynitrite promotes serine-62 phosphorylation-dependent stabilization of the oncoprotein c-Myc.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Mitochondrial superoxide dismutase controls metabolic plasticity in pancreatic cancer.Cell communication and signaling : CCS · 2025Article
- CircPVT1 Promotes Lung Metastasis and Tumor Progression in Renal Cell Carcinoma by Encoding the cP104aa Peptide and Targeting EIF4A3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Superoxide-mediated phosphorylation and stabilization of Mcl-1 by AKT underlie venetoclax resistance in hematologic malignancies.Leukemia · 2025Article
- AKR1B10 dictates c-Myc stability to suppress colorectal cancer metastasis via PP2A nitration.Science advances · 2025Article
- Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications.Redox biology · 2024Review
- The OGT-c-Myc-PDK2 axis rewires the TCA cycle and promotes colorectal tumor growth.Cell death and differentiation · 2024Article
- Targeting ROS in cancer: rationale and strategies.Nature reviews. Drug discovery · 2024Review
- Phosphoproteomic analysis reveals changes in A-Raf-related protein phosphorylation in response to Toxoplasma gondii infection in porcine macrophages.Parasites & vectors · 2024Article
- Melatonin regulates cancer migration and stemness and enhances the anti-tumour effect of cisplatin.Journal of cellular and molecular medicine · 2023Article
- Editorial: The proceedings of mitochondria apoptosis and cancer (MAC 2021) virtual symposium.Frontiers in cell and developmental biology · 2022Article
- Interplay between Mitochondrial Metabolism and Cellular Redox State Dictates Cancer Cell Survival.Oxidative medicine and cellular longevity · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stabilization of c-Myc oncoprotein is dependent on post-translational modifications, especially its phosphorylation at serine-62 (S62), which enhances its tumorigenic potential. Herein we report that increase in intracellular superoxide induces phospho-stabilization and activation of c-Myc in cancer cells. Importantly, sustained phospho-S62 c-Myc was necessary for promoting superoxide dependent chemoresistance as non-phosphorylatable S62A c-Myc was insensitive to the redox impact when subjected to chemotherapeutic insults. This redox-dependent sustained S62 phosphorylation occurs through nitrative inhibition of phosphatase, PP2A, brought about by peroxynitrite, a reaction product of superoxide and nitric oxide. We identified a conserved tyrosine residue (Y238) in the c-Myc targeting subunit B56α of PP2A, which is selectively amenable to nitrative inhibition, further preventing holoenzyme assembly. In summary, we have established a novel mechanism wherein the pro-oxidant microenvironment stimulates a pro-survival milieu and reinforces tumor maintenance as a functional consequence of c-Myc activation through its sustained S62 phosphorylation via inhibition of phosphatase PP2A. SIGNIFICANCE STATEMENT: Increased peroxynitrite signaling in tumors causes sustained S62 c-Myc phosphorylation by PP2A inhibition. This is critical to promoting c-Myc stabilization and activation which promotes chemoresistance and provides significant proliferative and growth advantages to osteosarcomas.
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