ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint
| Autor: | Chan Tian, Fengjie Yuan, Lina Wang, Nan Zhang, Dan Li, Xin Yang, Yuanshuai Song, Ying Zhao, Ximin Jin, Wei-Guo Zhu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cell cycle checkpoint
Mad1 Chromosomal Proteins Non-Histone Cell Cycle Proteins Spindle Apparatus Biology Chromosome segregation 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Chromosome Segregation Genetics Autophagy-Related Protein-1 Homolog Humans Phosphorylation Kinetochores Molecular Biology Mitosis 030304 developmental biology 0303 health sciences RZZ complex Kinetochore Cell Cycle Checkpoints HCT116 Cells Cell biology Spindle checkpoint ZW10 030220 oncology & carcinogenesis Microtubule-Associated Proteins HeLa Cells |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkz602 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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