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Title: ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins

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. In this study, 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.
Authors:
 [1] ;  [2] ;  [1] ;  [2] ;  [2] ;  [1] ;  [1] ;  [1] ;  [2] ;  [1]
  1. Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom
  2. Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
Publication Date:
Grant/Contract Number:
AC02-76SF00515
Type:
Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 4; Related Information: CHORUS Timestamp: 2018-08-23 10:40:34; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
OSTI Identifier:
1185249
Alternate Identifier(s):
OSTI ID: 1198491

Caballe, Anna, Wenzel, Dawn M., Agromayor, Monica, Alam, Steven L., Skalicky, Jack J., Kloc, Magdalena, Carlton, Jeremy G., Labrador, Leticia, Sundquist, Wesley I., and Martin-Serrano, Juan. ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins. United States: N. p., Web. doi:10.7554/eLife.06547.
Caballe, Anna, Wenzel, Dawn M., Agromayor, Monica, Alam, Steven L., Skalicky, Jack J., Kloc, Magdalena, Carlton, Jeremy G., Labrador, Leticia, Sundquist, Wesley I., & Martin-Serrano, Juan. ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins. United States. doi:10.7554/eLife.06547.
Caballe, Anna, Wenzel, Dawn M., Agromayor, Monica, Alam, Steven L., Skalicky, Jack J., Kloc, Magdalena, Carlton, Jeremy G., Labrador, Leticia, Sundquist, Wesley I., and Martin-Serrano, Juan. 2015. "ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins". United States. doi:10.7554/eLife.06547.
@article{osti_1185249,
title = {ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins},
author = {Caballe, Anna and Wenzel, Dawn M. and Agromayor, Monica and Alam, Steven L. and Skalicky, Jack J. and Kloc, Magdalena and Carlton, Jeremy G. and Labrador, Leticia and Sundquist, Wesley I. and Martin-Serrano, Juan},
abstractNote = {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. In this study, 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.},
doi = {10.7554/eLife.06547},
journal = {eLife},
number = ,
volume = 4,
place = {United States},
year = {2015},
month = {5}
}