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Formin-mediated nuclear actin at androgen receptors promotes transcription

Author

Listed:
  • Julian Knerr

    (University of Freiburg)

  • Ralf Werner

    (University of Lübeck
    University of Lübeck)

  • Carsten Schwan

    (University of Freiburg)

  • Hong Wang

    (University of Freiburg)

  • Peter Gebhardt

    (University of Freiburg)

  • Helga Grötsch

    (University of Lübeck
    Veraxa Biotech)

  • Almuth Caliebe

    (University Hospital Schleswig-Holstein, University of Lübeck and Kiel University, Lübeck)

  • Malte Spielmann

    (University Hospital Schleswig-Holstein, University of Lübeck and Kiel University, Lübeck
    Partner site Hamburg, Lübeck)

  • Paul-Martin Holterhus

    (University Hospital of Schleswig-Holstein)

  • Robert Grosse

    (University of Freiburg
    University of Freiburg)

  • Nadine C. Hornig

    (University Hospital Schleswig-Holstein, University of Lübeck and Kiel University, Lübeck)

Abstract

Steroid hormone receptors are ligand-binding transcription factors essential for mammalian physiology. The androgen receptor (AR) binds androgens mediating gene expression for sexual, somatic and behavioural functions, and is involved in various conditions including androgen insensitivity syndrome and prostate cancer1. Here we identified functional mutations in the formin and actin nucleator DAAM2 in patients with androgen insensitivity syndrome. DAAM2 was enriched in the nucleus, where its localization correlated with that of the AR to form actin-dependent transcriptional droplets in response to dihydrotestosterone. DAAM2 AR droplets ranged from 0.02 to 0.06 µm3 in size and associated with active RNA polymerase II. DAAM2 polymerized actin directly at the AR to promote droplet coalescence in a highly dynamic manner, and nuclear actin polymerization is required for prostate-specific antigen expression in cancer cells. Our data uncover signal-regulated nuclear actin assembly at a steroid hormone receptor necessary for transcription.

Suggested Citation

  • Julian Knerr & Ralf Werner & Carsten Schwan & Hong Wang & Peter Gebhardt & Helga Grötsch & Almuth Caliebe & Malte Spielmann & Paul-Martin Holterhus & Robert Grosse & Nadine C. Hornig, 2023. "Formin-mediated nuclear actin at androgen receptors promotes transcription," Nature, Nature, vol. 617(7961), pages 616-622, May.
  • Handle: RePEc:nat:nature:v:617:y:2023:i:7961:d:10.1038_s41586-023-05981-1
    DOI: 10.1038/s41586-023-05981-1
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    Cited by:

    1. Maria Dilia Palumbieri & Chiara Merigliano & Daniel González-Acosta & Danina Kuster & Jana Krietsch & Henriette Stoy & Thomas Känel & Svenja Ulferts & Bettina Welter & Joël Frey & Cyril Doerdelmann & , 2023. "Nuclear actin polymerization rapidly mediates replication fork remodeling upon stress by limiting PrimPol activity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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