Elucidation of the molecular mechanism of a novel response to microtubule-targeting agents and evaluation of their molecular as a potential therapeutic target.

2014 Fiscal Year Final Research Report

• 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
• Keywords: 微小管結合性抗癌剤 / 有糸分裂 / 微小管

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.

Free Research Field

細胞生物学