{
  "abstract": "Accurate chromosome segregation during mitosis requires the precise regulation of separase, a protease that cleaves cohesin to trigger the separation of sister chromatids. Here, we identify the AMPK-activating kinase Sak1 as a novel regulator of separase in Saccharomyces cerevisiae. Using a suppressor screen, we discovered a hypermorphic SAK1-E50K allele that restored separase activity and nuclear localization in esp1-2 and pds1Δ mutants. We demonstrated that Sak1 phosphorylates separase independently of Snf1 activation, enhancing its enzymatic function and promoting nuclear accumulation. Loss of Sak1 delays Cdc14 activation and phenocopies FEAR pathway defects, establishing Sak1 as a mitotic regulator. Extending these findings to humans, we demonstrated that human separase and the tumor suppressor kinase LKB1, which is homologous to Sak1, physically associate. This finding reveals an evolutionarily conserved regulatory link between LKB1 and separase, highlighting the kinase-protease interplay as a critical mechanism for ensuring faithful mitotic progression.",
  "abstract_shown": true,
  "affiliations": [
    "Instituto de Biomedicina de Valencia (IBV-CSIC) , Valencia, Spain.",
    "Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center , New York, NY, USA.",
    "Structure of Macromolecular Targets Unit, Instituto de Biomedicina de Valencia (IBV), CSIC, Valencia, Spain.",
    "Valencia Biomedical Research Foundation, Centro de Investigación Príncipe Felipe (CIPF), Associated Unit to the Instituto de Biomedicina de Valencia (IBV) , Valencia, Spain.",
    "Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona, Spain.",
    "Mechanisms of Disease Program, Institute for Research in Biomedicine (IRB), The Barcelona Institute of Science and Technology , Barcelona, Spain.",
    "ICREA, Pg. Lluis Companys 23 , Barcelona, Spain.",
    "Centro de Investigación Biomédica En Red de Enfermedades Infecciosas , Barcelona, Spain.",
    "National Horizons Centre, Teesside University , Darlington, UK.",
    "Centro de Investigacion Principe Felipe , Valencia, Spain."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "David Vaquero-Pelaz",
      "orcid": "0000-0002-9992-3619"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "José-Antonio Rodriguez-Rodriguez",
      "orcid": "0000-0002-5263-0210"
    },
    {
      "affs": [
        0
      ],
      "name": "Malina Carmina Ilinca",
      "orcid": "0000-0001-8105-1499"
    },
    {
      "affs": [
        0
      ],
      "name": "Esther Casas-Fernández",
      "orcid": "0009-0008-4652-4818"
    },
    {
      "affs": [
        0
      ],
      "name": "Amparo Picard",
      "orcid": "0000-0002-0871-5444"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Francisco Del Caño-Ochoa",
      "orcid": "0000-0003-3093-3103"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabel Vernia",
      "orcid": "0009-0000-8244-6767"
    },
    {
      "affs": [
        4,
        5,
        6,
        7
      ],
      "name": "Toni Gabaldón",
      "orcid": "0000-0003-0019-1735"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Maria Angeles Juanes",
      "orcid": "0000-0002-9801-9652"
    },
    {
      "affs": [
        0
      ],
      "name": "Ethel Queralt",
      "orcid": "0000-0003-0045-0039"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9511ff603s5v1.bib",
  "cited_by": 0,
  "doi": "10.1083/jcb.202505056",
  "fulltext_url": "https://europepmc.org/articles/PMC13682446",
  "id": "9511ff603s5v1",
  "issns": [
    "0021-9525",
    "1540-8140"
  ],
  "landing_url": "https://europepmc.org/article/MED/42900164",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1307|Microtubule and mitosis dynamics"
    ]
  ],
  "openalex": "W7223054558",
  "pdf_url": "https://europepmc.org/articles/PMC13682446?pdf=render",
  "pmcid": "PMC13682446",
  "pmid": "42900164",
  "published": "2026-10-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9511ff603s5v1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42900164",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42900164"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Microtubule and mitosis dynamics",
      "subfield": "cell-biology"
    }
  ],
  "title": "The AMPK kinase Sak1 activates separase and promotes its nuclear localization during mitosis.",
  "title_text": "The AMPK kinase Sak1 activates separase and promotes its nuclear localization during mitosis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/9511ff603s5v1",
  "venue": "The Journal of cell biology",
  "versions": []
}