The Tumor Suppressor Cdkn3 Is Required for Maintaining the Proper Number of Centrosomes by Regulating the Centrosomal Stability of Mps1
| Autor: | Mayumi Kitagawa, Jasmine Wong, Vinayaka Srinivas, Pei-Ju Liao, Sang Hyun Lee |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Proteasome Endopeptidase Complex
Cell Cycle Proteins Centrosome cycle Protein Serine-Threonine Kinases General Biochemistry Genetics and Molecular Biology spindle assembly checkpoint Cell Line law.invention law Dual-specificity phosphatase Humans Centrosome duplication Mps1 lcsh:QH301-705.5 Mitosis Cyclin-Dependent Kinase Inhibitor Proteins mitosis Centrosome biology Tumor Suppressor Proteins Cdkn3 Protein-Tyrosine Kinases Cell biology Spindle checkpoint centrosome duplication lcsh:Biology (General) biology.protein Dual-Specificity Phosphatases Suppressor Cyclin-dependent kinase inhibitor protein |
| Zdroj: | Cell Reports, Vol 13, Iss 8, Pp 1569-1577 (2015) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.10.039 |
| Popis: | SummarySupernumerary centrosomes promote the assembly of abnormal spindles in many human cancers. The observation that modest changes in the centrosomal levels of Mps1 kinase can cause centrosome overduplication in human cells suggests the existence of a regulatory system that may tightly control its centrosomal stability. Here, we show that Cdkn3, a Cdk-associated phosphatase, prevents Mps1-mediated centrosome overduplication. We identify Cdkn3 as a direct binding partner of Mps1. The interaction between Mps1 and Cdkn3 is required for Mps1 to recruit Cdkn3 to centrosomes. Subsequently, Mps1-bound Cdkn3 forms a regulatory system that controls the centrosomal levels of Mps1 through proteasome-mediated degradation and thereby prevents Mps1-mediated centrosome overduplication. Conversely, knockdown of Cdkn3 stabilizes Mps1 at centrosomes, which promotes centrosome overduplication. We suggest that Mps1 and Cdkn3 form a self-regulated feedback loop at centrosomes to tightly control the centrosomal levels of Mps1, which prevents centrosome overduplication in human cells. |
| Databáze: | OpenAIRE |
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