TAK1 kinase determines TRAIL sensitivity by modulating reactive oxygen species and cIAP

被引：0
作者：
S Morioka
E Omori
T Kajino
R Kajino-Sakamoto
K Matsumoto
J Ninomiya-Tsuji
机构：
[1] Graduate School of Science,Department of Molecular Biology
[2] Nagoya University,Department of Environmental and Molecular Toxicology
[3] North Carolina State University,undefined
[4] Solution Oriented Research for Science and Technology (SORST),undefined
[5] Japan Science and Technology Agency,undefined
来源：
Oncogene | 2009年 / 28卷
关键词：
TAK1; TRAIL; reactive oxygen species; cIAP; apoptosis;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
TNF-related apoptosis-inducing ligand (TRAIL) is a potent inducer of cell death in several cancer cells, but many cells are resistant to TRAIL. The mechanism that determines sensitivity to TRAIL-killing is still elusive. Here we report that deletion of TAK1 kinase greatly increased activation of caspase-3 and cell death after TRAIL stimulation in keratinocytes, fibroblasts and cancer cells. Although TAK1 kinase is involved in NF-κB pathway, ablation of NF-κB did not alter sensitivity to TRAIL. We found that TRAIL could induce accumulation of reactive oxygen species (ROS) when TAK1 was deleted. Furthermore, we found that TAK1 deletion induced TRAIL-dependent downregulation of cIAP, which enhanced activation of caspase-3. These results show that TAK1 deletion facilitates TRAIL-induced cell death by activating caspase through ROS and downregulation of cIAP. Thus, inhibition of TAK1 can be an effective approach to increase TRAIL sensitivity.
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页码：2257 / 2265
页数：8
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