Roles of Nedd4-IRS complexes in the development of diabetes and cancer

2017 Fiscal Year Final Research Report

• Project/Area Number: 26460369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tokyo Institute of Technology (2015-2017); Hiroshima University (2014)
• Principal Investigator: Fukushima Toshiaki 東京工業大学, 科学技術創成研究院, 助教 (70543552)
• Co-Investigator(Renkei-kenkyūsha): SAEKI Yasushi 東京都医学総合研究所, 蛋白質代謝研究室, 副参事研究員 (80462779) ; ITO Akihiro 東京薬科大学, 生命科学部, 教授 (40391859)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: インスリン / インスリン様成長因子 / インスリン受容体基質 / ユビキチン / がん / 糖尿病

Outline of Final Research Achievements

Insulin plays central roles in the regulation of glucose metabolism. Upon overnutrition, insulin target cells become resistant to insulin, and excessive resistance causes diabetes. Insulin-like growth factor (IGF) is a peptide similar in structure to insulin, and promotes body growth. Excessive sensitivity of cells to IGF contributes to hyper-proliferation and oncogenic transformation of cells. The mechanisms by which the responsiveness of cells to insulin/IGF is altered are not fully understood. In this study, we investigated intracellular signaling that is activated just after insulin/IGF binds to their membrane receptors. We found that IRS2, one of major insulin/IGF signal transducer proteins, associates with a protein called Nedd4. Our study indicated that the excessive disassembly of this Nedd4-IRS2 complex leads to insulin resistance and diabetes, whereas the excessive assembly contributes to hyper-proliferation of cancer cells.

Free Research Field

分子細胞生物学、分子内分泌学