{
  "id": 10711417,
  "title": "Cytokine-induced nuclear translocation of STAT1 via a non-transferable NLS",
  "url": "https://urgent.news/2026/09/29/cytokine-induced-nuclear-translocation-of-stat1-via-a-non",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-29T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.28.754937v1?rss=1"
  },
  "original_language": "en",
  "account": "Cytokines trigger a unique nuclear translocation of phosphorylated STAT1 (pSTAT1) that defies the common belief about the role of nuclear localization signals (NLSs). This process relies on importin {beta}, Ran-GTP, and the specific importin 5 isoform, which has its own non-transferable NLS target. Through cryo-EM structures, scientists reveal an unusual 2:1 complex formation between importin 5 and pSTAT1, where the latter's DNA-binding groove is occupied, causing a shift in the armadillo repeats (S1B domain) to face away from the DNA-binding area. This specific interface is also recognized by the Ebola virus protein VP24, a known inhibitor of interferon signaling. Moreover, Ran-GTP alone is not enough to release pSTAT1 into the nucleus; exportin CAS is also required. A cryo-EM reconstruction shows that both CAS and pSTAT1 exclusively bind to importin 5, with the two proteins mutually exclusive in their interaction with the importin 5 molecule. These findings provide a clear molecular description of the steps involved in cytokine-induced STAT1 nuclear translocation and release, forming a new standard for understanding the signaling processes within the STAT family.",
  "summary": "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…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}