{
  "abstract": "Melanoma therapies can produce substantial tumor regression without durable control, raising two separable questions: how efficiently tumor cells are eliminated and whether therapy-induced death supports immune recognition. This review examines whether melanocytic-lineage redox biology and site-selective protein S-nitrosylation help connect these outcomes. We distinguish mechanisms demonstrated directly in melanoma from mechanistic precedents in other systems and from hypotheses that require validation. In melanocytic cells, active pigment-forming chemistry can support a nitric oxide synthase (NOS)-active state. In melanoma, S-nitrosylation has been linked to MAPK persistence during MEK inhibition, TSC2-dependent mTOR activation, and NOS1-dependent suppression of interferon programs through HDAC2 and IRF7. Pharmacological S-nitrosylation blockade also increases ER stress signaling, calreticulin exposure, HMGB1 release, immune cell recruitment, and tumor control, but these observations do not establish a site-specific effect on the immunological quality of cell death. We therefore propose a two-gate framework in which S-nitrosylation may regulate both susceptibility to irreversible death and the signaling competence of dying cells. Establishing this model will require quantitative site occupancy, cell type-resolved nitrosoproteomics, causal site replacement, and immune assays that distinguish altered signaling from simply increased cell killing. The available evidence supports selective interrogation of causal S-nitrosylation nodes rather than indiscriminate suppression of NO biology.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA",
    "Corresponding author."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jyoti Srivastava"
    },
    {
      "affs": [
        1
      ],
      "name": "Sanjay Premi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ex0819hb0wmh9.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104401",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2213231726004003",
  "id": "ex0819hb0wmh9",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://doi.org/10.1016/j.redox.2026.104401",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "lcc",
      "R5-920"
    ],
    [
      "openalex",
      "1312|Redox biology and oxidative stress"
    ]
  ],
  "openalex": "W7212511523",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2213231726004003/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/ex0819hb0wmh9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10e3ecb93183405faf4cf8342c14e975",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.redox.2026.104401"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Redox biology and oxidative stress",
      "subfield": "molecular-biology"
    }
  ],
  "title": "S-nitrosylation topology in melanoma: established mechanisms, unresolved redox-immune links, and a testable framework",
  "title_text": "S-nitrosylation topology in melanoma: established mechanisms, unresolved redox-immune links, and a testable framework",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:15Z",
  "url": "https://research.draconitic.com/paper/ex0819hb0wmh9",
  "venue": "Redox Biology",
  "versions": []
}