ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins. Elife 2015 May 26;4:e06547
Date
05/27/2015Pubmed ID
26011858Pubmed Central ID
PMC4475061DOI
10.7554/eLife.06547Scopus ID
2-s2.0-84930631701 (requires institutional sign-in at Scopus site) 67 CitationsAbstract
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.
Author List
Caballe A, Wenzel DM, Agromayor M, Alam SL, Skalicky JJ, Kloc M, Carlton JG, Labrador L, Sundquist WI, Martin-Serrano JAuthor
Dawn M. Wenzel PhD Assistant Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cell LineCytokinesis
Endosomal Sorting Complexes Required for Transport
Humans
Oncogene Proteins
Phosphorylation
Protein Binding
Protein Processing, Post-Translational
