The seventh zinc finger motif of A20 is required for the suppression of TNF-α-induced apoptosis.
The ubiquitin-editing enzyme A20 suppresses nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α)-induced apoptosis in a deubiquitinating and ubiquitin ligase activity-dependent manner. Although recent studies revealed that A20 regulates NF-κB independently of its enzymatic activity through its seventh zinc finger motif (ZnF7), the involvement of ZnF7 in TNF-α-induced apoptosis is not clear. In this study, ZnF7 was found to be important for A20-mediated suppression of TNF-α-induced apoptosis. We also found that the ubiquitin ligases cIAP1/2 are required for A20 to suppress TNF-α-induced apoptosis. Because A20 binds to cIAP1/2 through ZnF7, these results suggest that A20 may control cIAP1/2 when suppressing TNF-α-induced apoptosis.
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan. Electronic address: yamaguchinoritaka@chiba-u.jp.
Noritaka
N
Yamaguchi
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Naoto
N
Yamaguchi
D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C508584:IL1A protein, human; D051034:Inhibitor of Apoptosis Proteins; D053582:Interleukin-1alpha; D047908:Intracellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011994:Recombinant Proteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C494833:BIRC2 protein, human; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; C494834:Birc2 protein, mouse; C494835:Birc3 protein, mouse; D044767:Ubiquitin-Protein Ligases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse
Apoptosis; Nuclear factor-κB; Tumor necrosis factor-α; Ubiquitin