Chemical Biological studies for autophagy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H03116
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Keio University
• Principal Investigator: IMOTO MASAYA 慶應義塾大学, 理工学部(矢上), 教授 (60213253)
• Co-Investigator(Kenkyū-buntansha): 斉木 臣二 順天堂大学, 医学部, 准教授 (00339996)
• Co-Investigator(Renkei-kenkyūsha): Tashiro Etsu 慶應義塾大学, 理工学部, 専任講師 (00365446)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: オートファジー

Outline of Final Research Achievements

We constructed GFP-LC3-RFP-expressing cells, and using the cells, we analyzed the diversity and consistency of regulatory signaling in autophagy. The effects of more than 200 small molecular compounds were assessed quantitatively by autophagy regulatory system in cancer cells and neuronal cells. Hierarchical clustering was performed on the subsequent autophagy inhibition profile of the compounds in each cell type. The result was that hierarchical clustering accurately classified the compounds according to their targets. And we distinguished between common and cell type-specific signals responsible for autophagy. SO286, which increased autophagy flux, inhibited the Aggresome formation. SO286 was found to bind SOBP, and by knockdown of SOBP, SO286 failed to inhibit Aggresome formation. This result indicated that SO286 functioned SOBP-dependent manner. We searched for the compounds that induce autophagic cell death, and we isolated Cholest-5-ene-3b,7a-diol from microbial origin.

Free Research Field

化学生物学