Requirement of c-Jun NH2-terminal kinase activation in interferon-alpha-induced apoptosis through upregulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Daudi B lymphoma cells.
Requirement of c-Jun NH2-terminal kinase activation in interferon-alpha-induced apoptosis through upregulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Daudi B lymphoma cells.
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DOI：
10.1016/j.yexcr.2005.06.021
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发表时间：
2005-10
影响因子：
3.7
通讯作者：
N. Yanase;Kikumi Hata;Kuniaki Shimo;Miho Hayashida;B. Evers;J. Mizuguchi
中科院分区：
文献类型：
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作者：
N. Yanase;Kikumi Hata;Kuniaki Shimo;Miho Hayashida;B. Evers;J. Mizuguchi
Interferon α (IFN-α) inhibits growth, at least in part, through induction of apoptosis. However, the molecular mechanisms underlying IFN-α-induced apoptosis are not completely understood. In the present study, we found that IFN-α induced a sustained activation of c-Jun N-terminal kinase 1 (JNK1), but not extracellular kinases (ERKs), in Daudi B lymphoma cells, as assessed by Western blotting using phospho-specific antibodies. Several lines of evidence support the notion that the IFN-α-induced activation of JNK is responsible for IFN-α-induced apoptosis, at least in part, through upregulation of TNF-related apoptosis-inducing ligand (TRAIL). First, pretreatment of Daudi cells with a JNK inhibitor reduced IFN-α-induced upregulation of TRAIL and loss of mitochondrial membrane potential (ΔΨm) and annexin-positive cells, which was assessed by flow cytometry. Second, a dominant-negative form of JNK1 (dnJNK1) also reduced these apoptotic events, while a constitutively active form of JNK1, MKK7-JNK1β, enhanced them. Finally, treatment with IFN-α enhanced the promoter activity of the TRAIL gene, which was partially abrogated by either JNK inhibitor or dnJNK1, while it was moderately enhanced by MKK7-JNK1β. These findings are useful for understanding molecular mechanisms of IFN-α-induced apoptosis and also for development of treatment modalities of some tumors with IFN-α.
