title: ATM kinase promotes both caspase-8 and caspase-9 activation during TNF-α-induced apoptosis of HeLa cells.
abstract: In this study, we show that atraxia telangiectasia mutated kinase (ATM) activity is generally upregulated by different apoptotic stimuli, i.e. TNF-α, TRAIL, paclitaxel, or UV. Apoptotic progression is markedly attenuated by siATM-RNA through down regulation of caspase-8 and caspase-9 in parallel with decreases in FLIP-S (short form of cellular FLICE inhibitory protein) protein levels and Bid cleavage. In addition, ATM activity is upregulated through t-Cdc6 while caspase-8 and caspase-9 activities increase. Taken together, we suggest that ATM regulates caspase-8 activation by influencing levels of FLIP-S, ATM kinase activity is upregulated by t-Cdc6, and increased ATM activity plays an essential role in the amplification of apoptosis in TNF-α-stimulated HeLa cells.
authors: Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian, 116044 Liaoning, China; Division of Pharmaceutical Biosciences, Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea. Electronic address: liulinhua@hotmail.com.
authors: Linhua
authors: L
authors: Liu
authors: Division of Pharmaceutical Biosciences, Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangrok-gu, Ansan, Kyeonggi-do 426-791, South Korea.
authors: Hyungshin
authors: H
authors: Yim
authors: Division of Pharmaceutical Biosciences, Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors: Jae Hyuk
authors: JH
authors: Choi
authors: Division of Pharmaceutical Biosciences, Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors: Seung-Tak
authors: ST
authors: Kim
authors: Department of Life Science, Jilin University, Jiefang Road, Changchun, China.
authors: Yinghua
authors: Y
authors: Jin
authors: Division of Pharmaceutical Biosciences, Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors: Seung Ki
authors: SK
authors: Lee
mesh_terms: D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
chemical_list: C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D017239:Paclitaxel
keywords: ATM; Cdc6; Mitochondria; TNF-α; c-FLIP