{
  "abstract": "The human HSP70 chaperone network maintains cellular proteostasis through a diverse repertoire of HSP70s and co-chaperones. Here we examine alternative isoforms and co-chaperone hetero-complexes as additional sources of network complexity. To that end, we systematically mapped the isoform, tissue-expression, and interaction landscapes of the human HSP70 network, revealing a modular interactome containing known and novel DNAJ-DNAJ interactions. We found both tissue-expression isoform divergence as well as widespread alternative-canonical isoform co-expression, suggesting additional modes of functional diversification. Focusing on the uncharacterized DNAJA2-DNAJA4 hetero-complex, we identified the stress-inducible isoform DNAJA4-CTD-II. DNAJA4-CTD-II formed hetero-complexes with DNAJA2 and DNAJA4, with both interactions enhanced following sodium arsenite stress. Functionally, DNAJA4-CTD-II co-localized with TDP-43 aggregates and significantly suppressed their accumulation in a DNAJA2-dependent manner. Together, our data reveal extensive, uncharted isoform and interaction complexity within the HSP70 network, and uncover isoform-dependent hetero-complex remodeling as a new layer of chaperone network regulation.",
  "abstract_shown": true,
  "affiliations": [
    "Technion - Israel Institute of Technology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "T. Kadah"
    },
    {
      "name": "N. Akaree"
    },
    {
      "name": "A. Brodov-Nevo"
    },
    {
      "name": "A. Meller"
    },
    {
      "name": "F. Levy-Adam"
    },
    {
      "affs": [
        0
      ],
      "name": "R. Shalgi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b88v3gf6m9t0z.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.23.753896",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753896v1.full",
  "id": "b88v3gf6m9t0z",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753896v1",
  "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",
      "systems biology"
    ],
    [
      "openalex",
      "1312|Heat shock proteins research"
    ]
  ],
  "openalex": "W7214161009",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753896v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b88v3gf6m9t0z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:22Z",
      "native_id": "10.64898/2026.09.23.753896",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753896v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:systems biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Chaperone isoform and interactome mapping reveals functional diversification of DNAJA2-DNAJA4 complexes via stress-regulated isoforms",
  "title_text": "Chaperone isoform and interactome mapping reveals functional diversification of DNAJA2-DNAJA4 complexes via stress-regulated isoforms",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:22Z",
  "url": "https://research.draconitic.com/paper/b88v3gf6m9t0z",
  "venue": "bioRxiv",
  "versions": []
}