Regulation of TRAIL-induced apoptosis by transcription factors.
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a newly identified member of the TNF family. Unlike many other members of the TNF family, TRAIL selectively induces apoptosis of tumor cells, but not normal cells. The mechanisms whereby TRAIL-induced apoptosis is regulated in various cell types are not clear. We report here that the peroxisome proliferator-activated receptor (PPAR)-gamma and nuclear factor (NF)-kappaB play distinct roles in regulating TRAIL-induced apoptosis. Activation of PPAR-gamma by its agonist pioglitazone significantly enhanced TRAIL-induced apoptosis. This was associated with inhibition of proliferation and cell cycle progression. On the other hand, inhibition of NF-kappaB by sulfasalazine also significantly enhanced TRAIL-induced apoptosis. These results strongly suggest that while transcription factor PPAR-gamma promotes TRAIL-induced apoptosis, NF-kappaB inhibits it. Thus, PPAR-gamma agonists and NF-kappaB inhibitors are potent enhancers of TRAIL-induced apoptosis.
Göke
R
R
Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Göke
A
A
Göke
B
B
Chen
Y
Y
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077205:Pioglitazone; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D012460:Sulfasalazine / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D000077205:Pioglitazone