論文 - 詳細
| RRC ID | 6600 |
|---|---|
| 著者 | Chiba S, Ikeda M, Katsunuma K, Ohashi K, Mizuno K. |
| タイトル | MST2- and Furry-mediated activation of NDR1 kinase is critical for precise alignment of mitotic chromosomes. |
| ジャーナル | Curr Biol |
| Abstract |
The precise alignment of chromosomes on the metaphase plate prior to the onset of anaphase is essential for ensuring equal segregation of sister chromatids into two daughter cells, and defects in this process potentially cause chromosome instability and tumor progression [1-3]. NDR1 is an evolutionarily conserved serine/threonine kinase whose activity is regulated by MST kinases, Furry (Fry), and MOB [4]. Although the NDR1 signaling pathway is implicated in cell division and morphogenesis in yeast and invertebrates [4-16], the mechanisms of NDR1 activation and the functional significance of the NDR1 pathway in mammalian cells are largely unknown. Here, we show that NDR1 is required for accurate chromosome alignment at metaphase in HeLa cells; depletion of NDR1, Fry, or MST2 caused mitotic chromosome misalignment. Chromosome misalignment in MST2-depleted cells was corrected by expression of active NDR1. The kinase activity of NDR1 increased in early mitotic phase and was dependent on Fry and MST2. We also provide evidence that Fry binds to microtubules, localizes on the spindle, acts as a scaffold that binds to both NDR1 and MOB2, and synergistically activates NDR1 with MOB2. Our findings suggest that MST2-, Fry-, and MOB2-mediated activation of NDR1 is crucial for the fidelity of mitotic chromosome alignment in mammalian cells. |
| 巻・号 | 19(8) |
| ページ | 675-81 |
| 公開日 | 2009-4-28 |
| DOI | 10.1016/j.cub.2009.02.054 |
| PII | S0960-9822(09)00807-0 |
| PMID | 19327996 |
| MeSH | Animals Cell Cycle Proteins Chromosomes, Human / metabolism* Drosophila HeLa Cells Humans Kinetochores / metabolism Metaphase / physiology* Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism* Nerve Tissue Proteins / metabolism Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Serine-Threonine Kinase 3 Signal Transduction / physiology Spindle Apparatus / metabolism |
| IF | 9.601 |
| 引用数 | 74 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | |