Research Project
Grant-in-Aid for Challenging Research (Exploratory)
The sumoylated MDM2 more largely expressed in cancer cells than in normal cells promoted the p53 degradation, which resulted in cancer progression. In this study, the plasmid to express fusion proteins consisting of SENP2 to specifically bind to sumoylated MDM2 and Hsc70bm to specifically bind to chaperone-mediated autophagy related Hsc70 was transfected into mammalian cells. Upon the transfection, the complex composed of sumoylated MDM2 and SENP2-Hsc70bm fusion protein and Hsc70 was transferred to the lysosome by chaperone-mediated autophagy, and the sumoylated MDM2 was significantly degraded in the lysosome without the p53 degradation. However, upon the transfection of the SENP2-Hsc70bm expression plasmid into tumor cells of mouse, the sumoylated MDM2 was degraded in a low level with the p53 degradation.
蛋白質の翻訳後修飾が破綻した異常翻訳後修飾は、細胞内シグナル伝達や細胞機能で異常を引き起こし、疾患発症と関連することが多く、異常翻訳後修飾蛋白質が原因である多くの疾患が見出されている。異常翻訳後修飾蛋白質が特異的に結合する配列と、Hsc70が特異的に結合する配列の融合蛋白質を発現するプラスミドを細胞に導入し、異常翻訳後修飾蛋白質を特異的に人工的に細胞内で分解する新規手法の開発に、本研究成果は端緒を与えた。
All 2020 2019 2018
All Journal Article (3 results) (of which Int'l Joint Research: 2 results, Peer Reviewed: 3 results, Open Access: 3 results) Presentation (6 results) (of which Invited: 1 results)
ChemBioChem
Volume: 21 Issue: 4 Pages: 517-522
10.1002/cbic.201900450
Sci.Rep.
Volume: 10 Issue: 1 Pages: 5388-5388
10.1038/s41598-020-62292-5
EMBO Molecular Medicine
Volume: 2018 Issue: 10 Pages: 1-21
10.15252/emmm.201809024
