{
  "abstract": "Wnt signaling controls cellular development by regulating levels of {beta}-catenin, a dual transcription factor and adhesion protein. The tumor suppressor gene Adenomatous Polyposis coli (APC) is a negative regulator of Wnt signaling that acts by interacting with multiple proteins in the destruction complex to drive {beta}-catenin degradation. Mutations in APC cause deregulation of Wnt/{beta}-catenin signaling contributing to the development of several types of cancer, especially colorectal cancers. Tumors are not null mutant for APC - instead they accumulate truncated proteins. Many APC proteins are truncated between the second and third 20-amino acid repeats, a region known as the {beta}-catenin inhibition domain (CID), which is essential for {beta}-catenin destruction, but its mechanism of action is unclear. Here we find that cyclin dependent kinases and GSK3{beta} phosphorylate the CID region of APC in vitro. This allows the APC CID to bind to the E3 ubiquitin ligase component {beta}-TrCP1 in a phosphorylation dependent manner and this in turn regulates the rate of {beta}-catenin ubiquitylation. {beta} TrCP1 binding to the phosphorylated CID favors the retention and stabilization of the SCF {beta}-TrCP1 E3 ligase in the destruction complex and ensures that SCF {beta}-TrCP1 remains available for {beta}-catenin ubiquitylation. These findings provide a mechanism for the vital role of APCs CID region in {beta}-catenin destruction.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "D. M. Johnston"
    },
    {
      "name": "C. L. Tarver"
    },
    {
      "name": "R. D. Leib"
    },
    {
      "name": "M. Koivomägi"
    },
    {
      "name": "F. Liu"
    },
    {
      "name": "C. M. Adams"
    },
    {
      "name": "W. I. Weis"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7jbarn1nwkx0y.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.16.751897",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751897v1.full",
  "id": "7jbarn1nwkx0y",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751897v1",
  "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",
      "biochemistry"
    ],
    [
      "openalex",
      "1312|Wnt/β-catenin signaling in development and cancer"
    ]
  ],
  "openalex": "W7213534706",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751897v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7jbarn1nwkx0y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:02Z",
      "native_id": "10.64898/2026.09.16.751897",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751897v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Wnt/β-catenin signaling in development and cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Phosphorylation-dependent binding of the Adenomatous Polyposis Coli protein to β-TrCP1 regulates β-catenin destruction",
  "title_text": "Phosphorylation-dependent binding of the Adenomatous Polyposis Coli protein to β-TrCP1 regulates β-catenin destruction",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:02Z",
  "url": "https://research.draconitic.com/paper/7jbarn1nwkx0y",
  "venue": "bioRxiv",
  "versions": []
}