[논문]An inducible system for in vitro and in vivo Fas activation using FKBP-FRB-rapamycin complex

Kim, Seokhwi; Shin, Jongpil; Oh, Hyunsik; Ahn, Sangphil; Kim, Nury; Heo, Won Do

doi:10.1016/j.bbrc.2019.12.072

[해외논문] An inducible system for in vitro and in vivo Fas activation using FKBP-FRB-rapamycin complex

Biochemical and biophysical research communications, v.523 no.2, 2020년, pp.473 - 480

Kim, Seokhwi (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)) , Shin, Jongpil (Department of Biological Sciences, KAIST) , Oh, Hyunsik (Department of Biological Sciences, KAIST) , Ahn, Sangphil (Department of Biological Sciences, KAIST) , Kim, Nury (Center for Cognition and Sociality, Institute for Basic Science (IBS)) , Heo, Won Do (Department of Biological Sciences, KAIST)

Abstract ▼ AI-Helper

Abstract The inducible activation system is valuable for investigating spatiotemporal roles of molecules. A chemically inducible activation system for Fas (CD95/APO-1), which works efficiently to induce apoptosis and leads non-apoptotic pathways, has not yet been developed. Here, we engineered a rapamycin-induced dimerization system of Fas consisting of FKBP and FRB proteins. Treatment of rapamycin specifically induces cellular apoptosis. In neurons and cells with high c-FLIP expression, rapamycin-induced Fas activation triggered the activation of the non-apoptotic pathway components instead of cell death. Intracranial delivery of the system could be utilized to induce apoptosis of tumor cells upon rapamycin treatment. Our results demonstrate a novel inducible Fas activation system which operates with high efficiency and temporal precision in vitro and in vivo promising a potential therapeutic strategy. Highlights Chemically inducible Fas activation system triggers apoptosis on rapamycin treatment. Caspases of apoptotic pathways are activated by rapamycin-induced Fas activation. Non-apoptotic pathway components can be activated by rapamycin-induced Fas activation. Rapamycin-induced Fas activation ablates tumor cells in vivo brain.

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