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ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint

The spindle assembly checkpoint (SAC) ensures the fidelity of chromosome segregation during mitosis. Here, we show that ULK1, a serine/threonine kinase that plays a key role in initiation of autophagy, also has an important function in the activation of SAC. ULK1 phosphorylates the SAC protein Mad1...

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Autores principales: Yuan, Fengjie, Jin, Ximin, Li, Dan, Song, Yuanshuai, Zhang, Nan, Yang, Xin, Wang, Lina, Zhu, Wei-Guo, Tian, Chan, Zhao, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736072/
https://www.ncbi.nlm.nih.gov/pubmed/31291454
http://dx.doi.org/10.1093/nar/gkz602
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author Yuan, Fengjie
Jin, Ximin
Li, Dan
Song, Yuanshuai
Zhang, Nan
Yang, Xin
Wang, Lina
Zhu, Wei-Guo
Tian, Chan
Zhao, Ying
author_facet Yuan, Fengjie
Jin, Ximin
Li, Dan
Song, Yuanshuai
Zhang, Nan
Yang, Xin
Wang, Lina
Zhu, Wei-Guo
Tian, Chan
Zhao, Ying
author_sort Yuan, Fengjie
collection PubMed
description The spindle assembly checkpoint (SAC) ensures the fidelity of chromosome segregation during mitosis. Here, we show that ULK1, a serine/threonine kinase that plays a key role in initiation of autophagy, also has an important function in the activation of SAC. ULK1 phosphorylates the SAC protein Mad1 at Ser546 to recruit Mad1 to kinetochores. Furthermore, Rod/ZW10/Zwilch (RZZ) complex may serve as a receptor for phos-Ser546-Mad1 at kinetochore, since phosphorylation of Mad1 by ULK1 strengthens the interaction between Mad1 and RZZ complex. In addition, deletion of ULK1 increases chromosome instability and cytotoxicity of paclitaxel, resulting in significant impairment of cancer cell growth. These findings highlight the role of ULK1 as a protein kinase controlling the fidelity of chromosome segregation and cell-cycle progression.
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spelling pubmed-67360722019-09-16 ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint Yuan, Fengjie Jin, Ximin Li, Dan Song, Yuanshuai Zhang, Nan Yang, Xin Wang, Lina Zhu, Wei-Guo Tian, Chan Zhao, Ying Nucleic Acids Res Molecular Biology The spindle assembly checkpoint (SAC) ensures the fidelity of chromosome segregation during mitosis. Here, we show that ULK1, a serine/threonine kinase that plays a key role in initiation of autophagy, also has an important function in the activation of SAC. ULK1 phosphorylates the SAC protein Mad1 at Ser546 to recruit Mad1 to kinetochores. Furthermore, Rod/ZW10/Zwilch (RZZ) complex may serve as a receptor for phos-Ser546-Mad1 at kinetochore, since phosphorylation of Mad1 by ULK1 strengthens the interaction between Mad1 and RZZ complex. In addition, deletion of ULK1 increases chromosome instability and cytotoxicity of paclitaxel, resulting in significant impairment of cancer cell growth. These findings highlight the role of ULK1 as a protein kinase controlling the fidelity of chromosome segregation and cell-cycle progression. Oxford University Press 2019-09-05 2019-07-10 /pmc/articles/PMC6736072/ /pubmed/31291454 http://dx.doi.org/10.1093/nar/gkz602 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Molecular Biology
Yuan, Fengjie
Jin, Ximin
Li, Dan
Song, Yuanshuai
Zhang, Nan
Yang, Xin
Wang, Lina
Zhu, Wei-Guo
Tian, Chan
Zhao, Ying
ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint
title ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint
title_full ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint
title_fullStr ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint
title_full_unstemmed ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint
title_short ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint
title_sort ulk1 phosphorylates mad1 to regulate spindle assembly checkpoint
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736072/
https://www.ncbi.nlm.nih.gov/pubmed/31291454
http://dx.doi.org/10.1093/nar/gkz602
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