Mask family proteins ANKHD1 and ANKRD17 regulate YAP nuclear import and stability

Abstract

Mask family proteins were discovered in Drosophila to promote the activity of the transcriptional coactivator Yorkie (Yki), the sole fly homolog of mammalian YAP (YAP1) and TAZ (WWTR1). The molecular function of Mask, or its mammalian homologs Mask1 (ANKHD1) and Mask2 (ANKRD17), remains unclear. Mask family proteins contain two ankyrin repeat domains that bind Yki/YAP as well as a conserved nuclear localisation sequence (NLS) and nuclear export sequence (NES), suggesting a role in nucleo-cytoplasmic transport. Here we show that Mask acts to promote nuclear import of Yki, and that addition of an ectopic NLS to Yki is sufficient to bypass the requirement for Mask in Yki-driven tissue growth. Mammalian Mask1/2 proteins also promote nuclear import of YAP, as well as stabilising YAP and driving formation of liquid droplets. Mask1/2 and YAP normally colocalise in a granular fashion in both nucleus and cytoplasm, and are co-regulated during mechanotransduction.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Clara Sidor

    Epithelial Biology Laboratory, Francis Crick Institute, London, United Kingdom
    For correspondence
    clara.sidor@univ-amu.fr
    Competing interests
    The authors declare that no competing interests exist.
  2. Nerea Borreguero-Munoz

    Epithelial Biology Laboratory, Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Georgina C Fletcher

    Epithelial Biology Laboratory, Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Ahmed Elbediwy

    Epithelial Biology Laboratory, Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2102-7339
  5. Oriane Guillermin

    Epithelial Biology Laboratory, Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Barry J Thompson

    Epithelial Biology Laboratory, Francis Crick Institute, London, United Kingdom
    For correspondence
    barry.thompson@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0103-040X

Funding

Wellcome (FC001180)

  • Barry J Thompson

Cancer Research UK (FC001180)

  • Barry J Thompson

Medical Research Council (FC001180)

  • Barry J Thompson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Roger J Davis, University of Massachusetts Medical School, United States

Publication history

  1. Received: May 20, 2019
  2. Accepted: October 29, 2019
  3. Accepted Manuscript published: October 29, 2019 (version 1)
  4. Version of Record published: November 18, 2019 (version 2)
  5. Version of Record updated: November 22, 2019 (version 3)

Copyright

© 2019, Sidor et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Clara Sidor
  2. Nerea Borreguero-Munoz
  3. Georgina C Fletcher
  4. Ahmed Elbediwy
  5. Oriane Guillermin
  6. Barry J Thompson
(2019)
Mask family proteins ANKHD1 and ANKRD17 regulate YAP nuclear import and stability
eLife 8:e48601.
https://doi.org/10.7554/eLife.48601

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