392회 Death promoting mechanism of Fas associated factor 1

392회

연사 : 김 은 희 , School of Bioscience & Biotechnology, Chungnam National University, Daejeon

제목:  Death promoting mechanism of Fas associated factor 1

Abstract

This study presents death promoting mechanism of Fas associated factor 1 (FAF1).  FAF1 induces cell death via extrinsic and intrinsic death pathways. FAF1 serves as a  member of Fas-death-inducing signaling complex (Fas-DISC) and potentiates Fas-mediated apoptosis. FAF1 suppresses NF-B activation by IKK activity attenuation and cytoplasmic retention of NF-B-p65. Therefore, FAF1 promotes cell death in two aspects i.e. lowering cell’s survival potential cells by supressing NF-B activity and potentiating apoptotic signal transduction as a member of Fas-DISC. FAF1 is also essential for the execution of ischemic cell death via caspase-independent cell death pathway (FAF1→ROS→PARP→AIF). Cell-based inhibitory compound screening identified a hit molecule (KR33196) targeting FAF1-mediated death pathway and its derivatives were synthesized and their efficacies were evaluated. KR-33196 demonstrated therapeutic potential as a novel anti-ischemic agent in MCAO model.