2016 Fiscal Year Final Research Report
Analysis on a novel checkpoint mechanism by which centrosomal kinases Lats1/2 regulate the chromosomal stability
| Project/Area Number |
26430112
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
NOJIMA Hiroshi 大阪大学, 微生物病研究所, 教授 (30156195)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 染色体不安定性 / キナーゼ / 中心体 / Lats / 細胞質分裂 / Hippo pathway / リン酸化 / チェックポイント |
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| Outline of Final Research Achievements |
Dysregulation of the centrosome cycle promotes the chromosomal instability (CIN), one of the hallmarks of tumor malignancy, thereby inducing centrosome overduplication, multipolar spindle formation, and chromosome missegregation. This suggests that certain centrosomal kinases stringently regulate the mitotic checkpoint. In this study, we found that the centrosomal kinases, Lats1 and Lats2, regulate centrosome duplication, cytokinesis, accurate chromosome segregation, and a nuclear function after DNA damage by phosphorylating various target proteins, such as Cdc25B, CHO1/MKLP1, and INCENP, thereby avoiding the induction of CIN. Therefore, we proposed a model in which the centrosomes function not only as a mitotic spindle pole for microtubule nucleation but also as an important site for crosstalk of signaling pathways in the mitotic checkpoint.
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| Free Research Field |
分子細胞生物学
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