Study on Molecular Mechanism of Cytotoxicity Concerning with Cytoskeleton

2015 Fiscal Year Final Research Report

• Project Area: Chemical Biology using bioactive natural products as specific ligands: identification of molecular targets and regulation of bioactivity
• Project/Area Number: 23102014
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: University of Tsukuba
• Principal Investigator: Kigoshi Hideo 筑波大学, 数理物質系, 教授 (90169839)
• Co-Investigator(Kenkyū-buntansha): HAYAKAWA Ichiro 筑波大学, 数理物質系, 助教 (20375413) ; KITA Masaki 筑波大学, 数理物質系, 准教授 (30335012)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 海洋天然物 / 抗腫瘍性 / アプリロニンＡ / 細胞骨格タンパク質 / アクチン / チューブリン / 三元複合体

Outline of Final Research Achievements

Potent antitumor marine macrolide aplyronine A firstly binds to actin, a kind of cytoskeletal protein. The 1:1 complex further binds to tubulin, another cytoskeletal protein. The ternary complex inhibits polymerization of tubulin, induces abnormal spindle, and induces apoptosis. This is the first example that antitumor compound induces protein-protein interaction between two major cytoskeletal proteins.

Free Research Field

生物有機化学