Requirement of c-Jun NH2-terminal kinase activation in interferon-α-induced apoptosis through upregulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Daudi B lymphoma cells

Noriko Yanase, Kikumi Hata, Kuniaki Shimo, Miho Hayashida, B. Mark Evers, Junichiro Mizuguchi

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)10-21
Number of pages12
JournalExperimental Cell Research
Volume310
Issue number1
DOIs
StatePublished - Oct 15 2005

Keywords

  • Apoptosis
  • B lymphocytes
  • Human
  • Interferon-α
  • Mitochondria
  • TRAIL
  • c-Jun NH2-Terminal Kinase

ASJC Scopus subject areas

  • Cell Biology

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