ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins
- King's College London School of Medicine, United Kingdom
- University of Utah School of Medicine, United States
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.
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© 2015, Caballe et al.
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ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins
eLife 4:e06547.
https://doi.org/10.7554/eLife.06547
