title: CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling.
abstract: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (Δψm), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS.
authors.affiliation: Laboratory of Cell Death and Human Diseases, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University Seoul, South Korea.
authors.forename: Jae Keun
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Laboratory of Cell Death and Human Diseases, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University Seoul, South Korea.
authors.forename: Sang Gil
authors.initials: SG
authors.lastname: Hwang
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University Seoul, South Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Molecular Biology, Sejong University Seoul, South Korea.
authors.forename: Jaekyung
authors.initials: J
authors.lastname: Shim
authors.affiliation: Laboratory of Cell Death and Human Diseases, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University Seoul, South Korea.
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
keywords: ALS (amyotrophic lateral sclerosis); ASK1 (apoptosis signal-regulating kinase 1); ROS (reactive oxygen species); cytotoxicity; mitochondria