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 CHMP...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/06547 |
| _version_ | 1818019602699911168 |
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| author | Anna Caballe Dawn M Wenzel Monica Agromayor Steven L Alam Jack J Skalicky Magdalena Kloc Jeremy G Carlton Leticia Labrador Wesley I Sundquist Juan Martin-Serrano |
| author_facet | Anna Caballe Dawn M Wenzel Monica Agromayor Steven L Alam Jack J Skalicky Magdalena Kloc Jeremy G Carlton Leticia Labrador Wesley I Sundquist Juan Martin-Serrano |
| author_sort | Anna Caballe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:54:30Z |
| format | Article |
| id | doaj.art-23974ee7fdd84e15b0829518c20720b4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:54:30Z |
| publishDate | 2015-05-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-23974ee7fdd84e15b0829518c20720b42022-12-22T02:05:06ZengeLife Sciences Publications LtdeLife2050-084X2015-05-01410.7554/eLife.06547ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteinsAnna Caballe0Dawn M Wenzel1Monica Agromayor2Steven L Alam3Jack J Skalicky4Magdalena Kloc5Jeremy G Carlton6Leticia Labrador7Wesley I Sundquist8Juan Martin-Serrano9Department of Infectious Diseases, King's College London School of Medicine, London, United KingdomDepartment of Biochemistry, University of Utah School of Medicine, Salt Lake City, United StatesDepartment of Infectious Diseases, King's College London School of Medicine, London, United KingdomDepartment of Biochemistry, University of Utah School of Medicine, Salt Lake City, United StatesDepartment of Biochemistry, University of Utah School of Medicine, Salt Lake City, United StatesDepartment of Infectious Diseases, King's College London School of Medicine, London, United KingdomDepartment of Infectious Diseases, King's College London School of Medicine, London, United KingdomDepartment of Infectious Diseases, King's College London School of Medicine, London, United KingdomDepartment of Biochemistry, University of Utah School of Medicine, Salt Lake City, United StatesDepartment of Infectious Diseases, King's College London School of Medicine, London, United KingdomThe 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.https://elifesciences.org/articles/06547cytokinesisabscission checkpointESCRTULK3phosphorylation |
| spellingShingle | Anna Caballe Dawn M Wenzel Monica Agromayor Steven L Alam Jack J Skalicky Magdalena Kloc Jeremy G Carlton Leticia Labrador Wesley I Sundquist Juan Martin-Serrano ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins eLife cytokinesis abscission checkpoint ESCRT ULK3 phosphorylation |
| title | ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins |
| title_full | ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins |
| title_fullStr | ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins |
| title_full_unstemmed | ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins |
| title_short | ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins |
| title_sort | ulk3 regulates cytokinetic abscission by phosphorylating escrt iii proteins |
| topic | cytokinesis abscission checkpoint ESCRT ULK3 phosphorylation |
| url | https://elifesciences.org/articles/06547 |
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