{
  "abstract": "The targeting function of nuclear localization signals (NLSs) is generally considered independent of a protein's native sequence or fold and is readily transferable to heterologous cargos. Contrary to this paradigm, rapid nuclear translocation of phosphorylated STAT1 (pSTAT1) following cytokine stimulation requires importin {beta}, Ran-GTP, and the importin 5 isoform, which recognizes a non-transferable NLS. Here, we present cryo-EM structures of pSTAT1 bound to importin 5, revealing an asymmetric 2:1 complex that diverges from canonical NLS-mediated cargo recognition. Importin 5 occupies the DNA-binding groove of the pSTAT1 dimer, with a single STAT1 N-terminal domain positioning the C-terminal Armadillo repeats 9-10 (S1B domain) orthogonal to the DNA-binding interface. This interface is also targeted by the Ebola virus protein VP24, an antagonist of interferon signaling. We further show that Ran-GTP alone is insufficient to trigger nuclear release of pSTAT1, which additionally requires the exportin CAS. A cryo-EM reconstruction of the CAS-Ran-GTP-5 complex, supported by in vitro competition assays, demonstrates that CAS and pSTAT1 are mutually exclusive ligands for importin 5. Together, these findings define the molecular choreography of cytokine-induced STAT1 nuclear translocation and release, establishing a general paradigm for STAT family signaling.",
  "abstract_shown": true,
  "affiliations": [
    "University of Alabama at Birmingham"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "P. Kumar"
    },
    {
      "name": "J. R. Cavey"
    },
    {
      "name": "R. Yang"
    },
    {
      "name": "O. White"
    },
    {
      "name": "A. Begitt"
    },
    {
      "name": "L. He"
    },
    {
      "name": "S. S. Suinn"
    },
    {
      "name": "N. F. Bellis"
    },
    {
      "name": "R. K. Lokareddy"
    },
    {
      "name": "U. Vinkemeier"
    },
    {
      "affs": [
        0
      ],
      "name": "G. Cingolani"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0m2e4wy7a6tmj.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.28.754937",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.754937v1.full",
  "id": "0m2e4wy7a6tmj",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.754937v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "1312|Nuclear Structure and Function"
    ]
  ],
  "openalex": "W7214754019",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.754937v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0m2e4wy7a6tmj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:08Z",
      "native_id": "10.64898/2026.09.28.754937",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.28.754937v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Nuclear Structure and Function",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Cytokine-induced nuclear translocation of STAT1 via a non-transferable NLS",
  "title_text": "Cytokine-induced nuclear translocation of STAT1 via a non-transferable NLS",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:08Z",
  "url": "https://research.draconitic.com/paper/0m2e4wy7a6tmj",
  "venue": "bioRxiv",
  "versions": []
}