Tumor necrosis factor: an apoptosis JuNKie?
TNF's main function is to stimulate inflammation by turning on gene transcription through the IKK/NFkappaB and JNK/AP-1 signaling cascades. TNF also can trigger apoptosis through caspase-8, but the role and underlying mechanism of this activity are not fully understood. Here, we review recent data on the role of JNK in the regulation of TNF-dependent apoptosis and discuss what is known so far about how cells decide whether to live or die in response to TNF.
Varfolomeev
Eugene E
EE
Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Ashkenazi
Avi
A
D000818:Animals; D017209:Apoptosis; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase; D007249:Inflammation; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D029721:Drosophila Proteins; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496563:IKKbeta protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases