Chromosomal dynamics and development of novel therapy in gastrointestinal tract cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462024
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: Saeki Hiroshi 九州大学, 医学(系)研究科(研究院), 准教授 (80325448)
• Co-Investigator(Kenkyū-buntansha): MORITA MASARU 独立行政法人国立病院機構, (九州がんセンター臨床研究センター), 統括診療部長 (30294937) ; KITAO HIROYUKI 九州大学, 医学研究院, 准教授 (30368617) ; OKI EIJI 九州大学, 大学病院, 講師 (70380392)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 染色体不安定性 / 集学的治療 / 消化管癌

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. Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at multiple sites within the amino 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 induces stable kinetochore microtubule dynamics and delays formation of bipolar metaphase plates in a microtubule binding-dependent manner, and leads to aneuploidy even in unperturbed mitosis. Aurora B and CDK1 temporally regulate the binding affinity of EB2 for microtubules, ensuring kinetochore microtubule dynamics, proper mitotic progression and genome stability.

Free Research Field

消化管外科