TNFalpha and reactive oxygen species in necrotic cell death.
Death receptors, including the TNF receptor-1 (TNF-RI), have been shown to be able to initiate caspase-independent cell death. This form of "necrotic cell death" appears to be dependent on the generation of reactive oxygen species. Recent data have indicated that superoxide generation is dependent on the activation of NADPH oxidases, which form a complex with the adaptor molecules RIP1 and TRADD. The mechanism of superoxide generation further establishes RIP1 as the central molecule in ROS production and cell death initiated by TNFalpha and other death receptors. A role for the sustained JNK activation in necrotic cell death is also suggested. The sensitization of virus-infected cells to TNFalpha indicates that necrotic cell death may represent an alternative cell death pathway for clearance of infected cells.
Morgan
Michael J
MJ
Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Kim
You-Sun
YS
Liu
Zheng-gang
ZG
D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009336:Necrosis / Q000378:metabolism / Q000473:pathology; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D053199:TNF Receptor-Associated Death Domain Protein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014777:Virus Diseases / Q000378:metabolism* / Q000473:pathology
C119724:AGFG1 protein, human; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D047888:Receptors, Tumor Necrosis Factor, Type I; D053199:TNF Receptor-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D019255:NADPH Oxidases; D048670:MAP Kinase Kinase 4