The regulatory mechanism of IRS monoubiquitination, a vital process regulating insulin/IGF signaling
| Project/Area Number |
17K08625
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | インスリン / IGF / シグナル伝達 / インスリン受容体基質 / ユビキチン / 糖尿病 / がん / インスリン様成長因子 / Nedd4 / USP / USP15 |
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| Outline of Final Research Achievements |
Insulin/insulin-like growth factors (IGFs) are essential for metabolic regulation and growth in animals. Abnormalities in the intracellular signals that they trigger in target cells can lead to the development of diabetes and cancer. In this study, we found that monoubiquitination levels of the insulin receptor substrate (IRS), which mediates the signals, are controlled by a ubiquitin ligase and deubiquitinating enzymes, thereby regulating the signal intensity by a novel mechanism. In addition, we clarified the molecular mechanism by which these enzymes recognize IRS as a substrate and the regulatory mechanism of enzyme activities.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は以前、インスリン/IGFの細胞内シグナルがIRSのモノユビキチン化によって制御されることを独自に発見していた。本研究では、この過程に関与するユビキチンリガーゼと脱ユビキチン化酵素を同定し、その作用機序を調べることで、研究を進展させた。本研究は、インスリン/IGFシグナルの新たな制御メカニズムの発見として、学術的価値が高い。また、同定した酵素を標的とすることで、インスリン/IGFシグナルを修飾する方法を開発できる可能性を示すことができた。この開発が成功すれば、糖尿病やがんの新しい治療法の開発につながると期待される。
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Report
(5 results)
Research Products
(41 results)
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[Journal Article] The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors2019
Author(s)
Sakai R, Fukuda R, Unida S, Aki M, Ono Y, Endo A, Kusumi S, Koga D, Fukushima T, Komada M, Okiyoneda T
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Journal Title
J Cell Sci.
Volume: 132
Issue: 3
Pages: 228007-228007
DOI
Related Report
Peer Reviewed
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[Journal Article] IRS-2 deubiquitination by USP9X maintains anchorage-independent cell growth via Erk1/2 activation in prostate carcinoma cell line.2018
Author(s)
Furuta Haruka, Yoshihara Hidehito, Fukushima Toshiaki, Yoneyama Yosuke, Ito Akihiro, Worrall Claire, Girnita Ada, Girnita Leonard, Yoshida Minoru, Asano Tomoichiro, Komada Masayuki, Kataoka Naoyuki, Chida Kazuhiro, Hakuno Fumihiko, Takahashi Shin-Ichiro
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Journal Title
Oncotarget
Volume: 9(74)
Issue: 74
Pages: 33871-33883
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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