title: Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities.
abstract: Diverse stimuli initiate the activation of apoptotic signaling pathways that often causes nuclear DNA fragmentation. Here, we report a new antiapoptotic protein, a caspase-activated DNase (CAD) inhibitor that interacts with ASK1 (CIIA). CIIA, by binding to apoptosis signal-regulating kinase 1 (ASK1), inhibits oligomerization-induced ASK1 activation. CIIA also associates with CAD and inhibits the nuclease activity of CAD without affecting caspase-3-mediated ICAD cleavage. Overexpressed CIIA reduces H2O2- and tumor necrosis factor-alpha-induced apoptosis. CIIA antisense oligonucleotides, which abolish expression of endogenous CIIA in murine L929 cells, block the inhibitory effect of CIIA on ASK1 activation, deoxyribonucleic acid fragmentation, and apoptosis. These findings suggest that CIIA is an endogenous antagonist of both ASK1- and CAD-mediated signaling.
authors.affiliation: Graduate School of Biotechnology, Korea University, Seoul 136-701, Korea.
authors.forename: Ssang-Goo
authors.initials: SG
authors.lastname: Cho
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Yong Hee
authors.initials: YH
authors.lastname: Lee
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Hwang
authors.forename: Mi-Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: Kanghyun
authors.initials: K
authors.lastname: Ryoo
authors.forename: Myung Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Noh
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Cho
authors.forename: Kyoung Wan
authors.initials: KW
authors.lastname: Yoon
authors.forename: Eun-Gyung
authors.initials: EG
authors.lastname: Cho
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Chi
authors.forename: Min-Jae
authors.initials: MJ
authors.lastname: Lee
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Kang
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053938:DNA Fragmentation / Q000502:physiology; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors*; D006861:Hydrogen Peroxide / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016376:Oligonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases; C482859:Map3k5 protein, mouse; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease