{
  "abstract": "Proteins are often classified as toxic or non-toxic without measuring the abundance reached, leaving constraints on tolerable protein abundance unresolved. We established a limit-pushing approach in Saccharomyces cerevisiae combining strong inducible expression with gTOW-mediated high-copy selection to counteract copy-number compensation while measuring protein abundance and growth. Nearly all of approximately 80 chromosome I proteins severely inhibited growth or reduced viability at sufficiently high abundance. We established IE50, the expression level associated with a 50% reduction in growth rate, to quantify their widely varying overexpression tolerance. IE50 was positively associated with predicted structural order and cytoplasmic localization propensity and negatively associated with sulphur content. Single-cell imaging linked higher tolerance to proteins remaining cytoplasmic without becoming aggregation-positive and revealed abundance-dependent changes in localization and organelle morphology. At extreme abundance, Fun12, Nup60, and Pex22 generated distinct large-scale intracellular states through specific sequence regions. These findings establish overexpression toxicity as a quantitative property linked to protein characteristics and reveal both constraints on tolerable abundance and sequence-dependent capacities for intracellular organization.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Environmental, Life, Natural Science and Technology, Okayama University, Okayama, Japan"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "S. Namba"
    },
    {
      "name": "Y. Nishida"
    },
    {
      "name": "C. Boone"
    },
    {
      "name": "B. Andrews"
    },
    {
      "affs": [
        0
      ],
      "name": "H. Moriya"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/en4pfep7ffvwg.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754258",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754258v1.full",
  "id": "en4pfep7ffvwg",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754258v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "systems biology"
    ],
    [
      "openalex",
      "1312|Fungal and yeast genetics research"
    ]
  ],
  "openalex": "W7214643098",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754258v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/en4pfep7ffvwg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:46Z",
      "native_id": "10.64898/2026.09.24.754258",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754258v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:systems biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Limit-pushing overexpression reveals constraints on protein abundance",
  "title_text": "Limit-pushing overexpression reveals constraints on protein abundance",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:46Z",
  "url": "https://research.draconitic.com/paper/en4pfep7ffvwg",
  "venue": "bioRxiv",
  "versions": []
}