title: cIAPs promote the proteasomal degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis.
abstract: Although the ubiquitin-proteasome system is believed to play an important role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS), caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1), the mechanism of how mutant SOD1 protein is regulated in cells is still poorly understood. Here we have demonstrated that cellular inhibitor of apoptosis proteins (cIAPs) are specifically associated with FALS-linked mutant SOD1 (mSOD1) and that this interaction promotes the ubiquitin-dependent proteasomal degradation of mutant SOD1. By utilizing cumate inducible SOD1 cells, we also showed that knock-down or pharmacologic depletion of cIAPs leads to H2O2induced cytotoxicity in mSOD1 expressing cells. Altogether, our results reveal a novel role of cIAPs in FALS-associated mutant SOD1 regulation.
authors: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 305-333, Republic of Korea.
authors: Jin Sun
authors: JS
authors: Choi
authors: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 305-333, Republic of Korea; Department of Bio-Analytical Science, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea.
authors: Kidae
authors: K
authors: Kim
authors: Department of Biotechnology, Seoul Women's University, Seoul, Republic of Korea.
authors: Do Hee
authors: DH
authors: Lee
authors: College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
authors: Sayeon
authors: S
authors: Cho
authors: Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong, Daejeon 305-600, Republic of Korea.
authors: Jae Du
authors: JD
authors: Ha
authors: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 305-333, Republic of Korea; Department of Bio-Analytical Science, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea.
authors: Byoung Chul
authors: BC
authors: Park
authors: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 305-333, Republic of Korea; Department of Biomolecular Science, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea. Electronic address: sunhong@kribb.re.kr.
authors: Sunhong
authors: S
authors: Kim
authors: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 305-333, Republic of Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea. Electronic address: sgpark@kribb.re.kr.
authors: Sung Goo
authors: SG
authors: Park
authors: Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 305-333, Republic of Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305-350, Republic of Korea. Electronic address: jhoonkim@kribb.re.kr.
authors: Jeong-Hoon
authors: JH
authors: Kim
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D000072105:Superoxide Dismutase-1 / Q000235:genetics* / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D051034:Inhibitor of Apoptosis Proteins; C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1; D046988:Proteasome Endopeptidase Complex
keywords: FALS; SOD1; Ubiquitination; cIAPs