1. Biochemistry and Chemical Biology
  2. Cell Biology
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ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins

  1. Anna Caballe
  2. Dawn M Wenzel
  3. Monica Agromayor
  4. Steven L Alam
  5. Jack J Skalicky
  6. Magdalena Kloc
  7. Jeremy G Carlton
  8. Leticia Labrador
  9. Wesley I Sundquist
  10. Juan Martin-Serrano  Is a corresponding author
  1. King's College London School of Medicine, United Kingdom
  2. University of Utah School of Medicine, United States
Research Article
  • Cited 55
  • Views 3,830
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Cite this article as: eLife 2015;4:e06547 doi: 10.7554/eLife.06547

Abstract

The Endosomal Sorting Complexes Required for Transport (ESCRT) machinery mediates the physical separation between daughter cells during cytokinetic abscission. This process is regulated by the abscission checkpoint, a genome protection mechanism that relies on Aurora B and the ESCRT-III subunit CHMP4C to delay abscission in response to chromosome missegregation. Here we show that Unc-51-like kinase 3 (ULK3) phosphorylates and binds ESCRT-III subunits via tandem MIT domains and thereby delays abscission in response to lagging chromosomes, nuclear pore defects and tension forces at the midbody. Our structural and biochemical studies reveal an unusually tight interaction between ULK3 and IST1, an ESCRT-III subunit required for abscission. We also demonstrate that IST1 phosphorylation by ULK3 is an essential signal required to sustain the abscission checkpoint and that ULK3 and CHMP4C are functionally linked components of the timer that controls abscission in multiple physiological situations.

Article and author information

Author details

  1. Anna Caballe

    Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom
    Competing interests
    No competing interests declared.
  2. Dawn M Wenzel

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  3. Monica Agromayor

    Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Steven L Alam

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  5. Jack J Skalicky

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  6. Magdalena Kloc

    Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom
    Competing interests
    No competing interests declared.
  7. Jeremy G Carlton

    Division of Cancer Studies, King's College London School of Medicine, London, United Kingdom
    Competing interests
    No competing interests declared.
  8. Leticia Labrador

    Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom
    Competing interests
    No competing interests declared.
  9. Wesley I Sundquist

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    Wesley I Sundquist, Reviewing editor, eLife.
  10. Juan Martin-Serrano

    Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom
    For correspondence
    juan.martin_serrano@kcl.ac.uk
    Competing interests
    No competing interests declared.

Reviewing Editor

  1. Mohan Balasubramanian, University of Warwick, United Kingdom

Publication history

  1. Received: January 18, 2015
  2. Accepted: May 23, 2015
  3. Accepted Manuscript published: May 26, 2015 (version 1)
  4. Version of Record published: June 22, 2015 (version 2)

Copyright

© 2015, Caballe 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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