{
  "abstract": "Coenzyme A (CoA) is an essential metabolic cofactor whose biosynthesis is controlled by pantothenate kinases (PANKs), the rate-limiting enzymes in CoA synthesis. Although CoA production is extensively regulated, whether PANK abundance is controlled by selective protein degradation remains unknown. Here, we identify PANK1{beta} and PANK3 as substrates of the Arg/N-degron pathway. Two mechanistically distinct E3 ligase systems, UBR4-KCMF1 and MKLN1-CTLH, independently converge on a common N-terminal MK Arg/N-degron to promote PANK degradation and restrict CoA biosynthesis. UBR4-KCMF1 recognizes the MK Arg/N-degron through KCMF1 ZZ domain, whereas CTLH complex employs the B30.2-domain proteins RanBP9 and RanBP10 as previously unrecognized Arg/N-degron recognins. Structural, biochemical, and cellular analyses demonstrate that RanBP9 and RanBP10 recognize both Met-X and canonical Arg/N-degrons through their B30.2 domains, using a mechanism distinct from canonical UBR proteins. Together, these findings establish a new branch of the mammalian Arg/N-degron pathway and reveal ubiquitin-dependent control of PANK abundance in CoA homeostasis.",
  "abstract_shown": true,
  "affiliations": [
    "Tianjin Medical University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "X. Wang"
    },
    {
      "name": "B. Wang"
    },
    {
      "name": "L. Zhang"
    },
    {
      "name": "S. Yan"
    },
    {
      "name": "N. Zhao"
    },
    {
      "name": "Y. Zhao"
    },
    {
      "name": "F. Shi"
    },
    {
      "name": "S. Yin"
    },
    {
      "name": "D. Chen"
    },
    {
      "name": "Y. Yu"
    },
    {
      "name": "C. Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "W. Mi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/26fgeb8wm7afw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.15.751905",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751905v1.full",
  "id": "26fgeb8wm7afw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751905v1",
  "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",
      "molecular biology"
    ],
    [
      "openalex",
      "1312|Ubiquitin and proteasome pathways"
    ]
  ],
  "openalex": "W7213500297",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751905v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/26fgeb8wm7afw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:55Z",
      "native_id": "10.64898/2026.09.15.751905",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751905v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Parallel Arg/N-degron recognition systems regulate coenzyme A biosynthesis",
  "title_text": "Parallel Arg/N-degron recognition systems regulate coenzyme A biosynthesis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:55Z",
  "url": "https://research.draconitic.com/paper/26fgeb8wm7afw",
  "venue": "bioRxiv",
  "versions": []
}