---
APC_amount: 7068 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '20929'
abstract:
- lang: eng
  text: Insulin/insulin-like growth factor signaling inhibits FOXO transcription factors
    to control development, homeostasis, and aging. Here, we use proximity labeling
    to identify proteins interacting with the C. elegans FOXO DAF-16. We show that
    in well-fed, unstressed animals harboring active insulin signaling, DAF-16 forms
    a complex with the PAR-1/MARK serine/threonine kinase, a key regulator of cell
    polarity. PAR-1 inhibits DAF-16 accumulation and promotes DAF-16 phosphorylation
    at S249, at a conserved motif that PAR-1/human MARK2 phosphorylates in vitro.
    DAF-2 insulin-like receptor signaling stimulates DAF-16 S249 phosphorylation,
    suggesting DAF-2 activates PAR-1. DAF-2 also promotes PAR-1 expression by inhibiting
    DAF-16. PAR-1 knockdown, or DAF-16 S249A, prolong lifespan, whereas phosphomimetic
    DAF-16 S249D suppresses the longevity of daf-2 mutants. At low insulin signaling,
    DAF-16 proximity labeling highlights transcription factors, chromatin regulators,
    and DNA repair proteins. One interactor, the zinc finger/homeobox protein ZFH-2/ZFHX3,
    forms a complex with DAF-16 and prolongs lifespan. Our work provides entry points
    for hypothesis-driven studies of FOXO function and longevity.
acknowledged_ssus:
- _id: Bio
acknowledgement: We thank de Bono lab members for helpful comments on the manuscript,
  and the Mass Spec Facility at the Max Perutz Labs, notably WeiQiang Chen and Markus
  Hartl, for invaluable discussions and comments on mass spec analyses of worm samples.
  All LC-MS/MS analyses were performed on instruments of the Vienna BioCenter Core
  Facilities (VBCF). Microscopy was supported by the Scientific Services Units (SSU)
  of ISTA through resources provided by the Imaging & Optics Facility (IOF). We are
  grateful to Dr. Geraldine Seydoux (Johns Hopkins University) for worm strains and
  plasmids, and Dr. Seung-Jae V. Lee (KAIST) for RNAi clones. We are grateful to Ekaterina
  Lashmanova for designing the daf-16::TbID::mNG::3xFLAG knock-in construct and for
  her outstanding support in the lab. This work was supported by a Wellcome Investigator
  Award (209504/A/17/Z) to MdB and an ISTplus Fellowship to MA (Marie Sklodowska-Curie
  agreement No 754411).
article_number: '11355'
article_processing_charge: Yes
article_type: original
author:
- first_name: Murat
  full_name: Artan, Murat
  id: C407B586-6052-11E9-B3AE-7006E6697425
  last_name: Artan
  orcid: 0000-0001-8945-6992
- first_name: Hanna
  full_name: Schön, Hanna
  id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425
  last_name: Schön
- first_name: Mario
  full_name: De Bono, Mario
  id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
  last_name: De Bono
  orcid: 0000-0001-8347-0443
citation:
  ama: Artan M, Schön H, de Bono M. Proximity labeling of DAF-16 FOXO highlights aging
    regulatory proteins. <i>Nature Communications</i>. 2025;16. doi:<a href="https://doi.org/10.1038/s41467-025-66409-0">10.1038/s41467-025-66409-0</a>
  apa: Artan, M., Schön, H., &#38; de Bono, M. (2025). Proximity labeling of DAF-16
    FOXO highlights aging regulatory proteins. <i>Nature Communications</i>. Springer
    Nature. <a href="https://doi.org/10.1038/s41467-025-66409-0">https://doi.org/10.1038/s41467-025-66409-0</a>
  chicago: Artan, Murat, Hanna Schön, and Mario de Bono. “Proximity Labeling of DAF-16
    FOXO Highlights Aging Regulatory Proteins.” <i>Nature Communications</i>. Springer
    Nature, 2025. <a href="https://doi.org/10.1038/s41467-025-66409-0">https://doi.org/10.1038/s41467-025-66409-0</a>.
  ieee: M. Artan, H. Schön, and M. de Bono, “Proximity labeling of DAF-16 FOXO highlights
    aging regulatory proteins,” <i>Nature Communications</i>, vol. 16. Springer Nature,
    2025.
  ista: Artan M, Schön H, de Bono M. 2025. Proximity labeling of DAF-16 FOXO highlights
    aging regulatory proteins. Nature Communications. 16, 11355.
  mla: Artan, Murat, et al. “Proximity Labeling of DAF-16 FOXO Highlights Aging Regulatory
    Proteins.” <i>Nature Communications</i>, vol. 16, 11355, Springer Nature, 2025,
    doi:<a href="https://doi.org/10.1038/s41467-025-66409-0">10.1038/s41467-025-66409-0</a>.
  short: M. Artan, H. Schön, M. de Bono, Nature Communications 16 (2025).
corr_author: '1'
date_created: 2026-01-04T23:01:34Z
date_published: 2025-12-11T00:00:00Z
date_updated: 2026-05-20T08:10:18Z
day: '11'
ddc:
- '570'
department:
- _id: MaDe
doi: 10.1038/s41467-025-66409-0
ec_funded: 1
external_id:
  pmid:
  - '41381452'
file:
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  creator: dernst
  date_created: 2026-01-05T10:58:28Z
  date_updated: 2026-01-05T10:58:28Z
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fulldoi: https://doi.org/10.1038/s41467-025-66409-0
has_accepted_license: '1'
intvolume: '        16'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 23870BE8-32DE-11EA-91FC-C7463DDC885E
  grant_number: 209504/A/17/Z
  name: Molecular mechanisms of neural circuit function
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2025'
...