{
  "abstract": "The accumulation of insoluble tau aggregates is a pathological hallmark of tauopathies, including Alzheimer's disease. While molecular chaperones and clearance pathways regulate tau homeostasis, the mechanisms governing tau oligomerization and degradation remain incompletely defined. Recent genome-wide association studies (GWAS) have linked the JADE1 locus to tauopathy, and the PHD zinc finger protein Jade1S has been identified in complexes with tau in post-mortem brain tissue, prompting investigation into their biochemical relationship. Here, we characterize the reciprocal interactions between Jade1S and 0N4R tau stability and turnover. Covalent labeling mass spectrometry and co-immunoprecipitation mappings reveal that Jade1S binds wild-type 0N4R tau through redundant sites within its N-terminal and plant homeodomain (PHD) zinc finger domains. In vitro assays demonstrate that Jade1S functions as a SUMO E3 ligase, utilizing its PHD domains to mediate tau SUMOylation. Cell-based cycloheximide chase assays reveal a reciprocal stabilization dynamic: tau co-expression extends the overall physiological half-life of Jade1S from less than an hour to ~17 hours, arresting its turnover specifically within sarkosyl-insoluble fractions. Conversely, Jade1S selectively accelerates the degradation of sarkosyl-insoluble tau without altering the turnover of the soluble monomeric pool over chased time. Mechanistically, Jade1S redirects the clearance of SUMO2/3-modified tau oligomers away from basal autophagic-lysosomal pathways and toward proteasome-dependent degradation. Furthermore, Jade1S exhibits intrinsic molecular chaperone activity, inhibiting arachidonic acid-induced tau oligomerization in vitro. Together, these data characterize Jade1S as a dual-function SUMO ligase and chaperone that regulates tau stability, prevents oligomer assembly, and promotes the targeted proteasomal clearance of aggregated tau.",
  "abstract_shown": true,
  "affiliations": [
    "Icahn School of Medicine at Mount Sinai"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "S. H. Kim"
    },
    {
      "name": "V. L. Stahl"
    },
    {
      "name": "L. Zou"
    },
    {
      "name": "S. Hassan"
    },
    {
      "name": "H. T. Cohen"
    },
    {
      "name": "K. Farrell"
    },
    {
      "name": "R. W. Vachet"
    },
    {
      "name": "J. N. Rauch"
    },
    {
      "affs": [
        0
      ],
      "name": "J. F. Crary"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d45122tvysz8v.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.764021",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764021v1.full",
  "id": "d45122tvysz8v",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764021v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764021v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d45122tvysz8v.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:42Z",
      "native_id": "10.64898/2026.11.03.764021",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764021v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biochemistry",
      "subfield": "general"
    }
  ],
  "title": "Jade1S SUMOylates tau and targets oligomers for degradation",
  "title_text": "Jade1S SUMOylates tau and targets oligomers for degradation",
  "type": "preprint",
  "updated_at": "2026-11-07T00:20:54Z",
  "url": "https://research.draconitic.com/paper/d45122tvysz8v",
  "venue": "bioRxiv",
  "versions": []
}