TRAIL-induced caspase/p38 activation is responsible for the increased catalytic and invasive activities of Akt.
TRAIL-induced caspase/p38 activation is responsible for the increased catalytic and invasive activities of Akt.
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DOI：
10.3892/ijo-00000845
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发表时间：
2010-12
影响因子：
5.2
通讯作者：
B. Sun;Joo‐Hang Kim;H. N. Nguyen;S. Kim;Seeun Oh;Yong J. Lee;Jae J. Song
中科院分区：
文献类型：
--
作者：
B. Sun;Joo‐Hang Kim;H. N. Nguyen;S. Kim;Seeun Oh;Yong J. Lee;Jae J. Song
We previously observed that TRAIL induces acquired TRAIL resistance coinciding with increased Akt phosphorylation brought about by the Src-PI3K-Akt signaling pathways and mediated by c-Cbl. c-Cbl, a ubiquitously expressed cytoplasmic adaptor protein, is simultaneously involved in the rapid degradation of TRAIL receptors and Akt phosphorylation during TRAIL treatment. Here, we show that Akt phosphorylation is not exclusively responsible for acquired TRAIL resistance. Akt catalytic activation is known to increase during metabolic oxidative stress, but we show that TRAIL also dramatically induces the catalytic activation of Akt in TRAIL-sensitive cells, but not in TRAIL-resistant cells. This suggests that Akt catalytic activation during TRAIL-induced apoptosis is likely to play a compensatory role in the maintenance of cell homeostasis. In addition, activated p38 and phosphorylated HSP27 were found to act as downstream effector molecules of p38 during TRAIL treatment and were shown to be responsible for increased Akt catalytic and invasive activities.
