| Project/Area Number |
25870501
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Tumor therapeutics
Tumor biology
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
IIMORI Makoto 九州大学, 医学(系)研究科(研究院), 助教 (20546460)
|
|---|
| Project Period (FY) |
2013-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | 微小管結合性抗癌剤 / 有糸分裂 / 微小管 / Aurora B / EB2 / ゲノム不安定性 / 有糸分裂期 / ゲノム安定性 |
|---|
| Outline of Final Research Achievements |
Temporal regulation of microtubule dynamics is essential for proper progression of mitosis, and control of microtubule plus-end tracking proteins by phosphorylation is an essential component of this regulation. Here we show that Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at multiple sites within the N-terminus and a cluster of serine/threonine residues in the linker connecting the calponin homology and end-binding homology domains. EB2 phosphorylation, which is strictly associated with mitotic entry and progression, reduces the binding affinity of EB2 for microtubules. Expression of non-phosphorylatable EB2 delayed formation of bipolar metaphase plates in a microtubule binding-dependent manner, and led to aneuploidy even in unperturbed mitosis. We propose that Aurora B and CDK1 temporally regulate EB2, as a downstream target of the spindle assembly checkpoint, thereby ensuring proper mitotic progression and genome stability.
|
