PKC-δ mediates interferon-α-induced apoptosis through c-Jun NH2-terminal kinase activation.
BMC Cell Biol
; 13: 7, 2012 Mar 21.
Article
en En
| MEDLINE
| ID: mdl-22435755
ABSTRACT
BACKGROUND:
Interferon-α (IFN-α) exerts an anti-tumor effect at least through induction of apoptosis in a variety of types including B lymphoma cells. We recently found that IFN-α induced a sustained activation of c-Jun NH2-terminal kinase1 (JNK1), which is implicated in activation of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) promoter. In the present study, we explored upstream component(s) of the prolonged IFN-α-initiated activation of JNK1.RESULTS:
IFN-α caused activation of PKC-δ in Daudi B lymphoma cells and myeloma U266 cells, as detected by Western blotting using a monoclonal antibody specific for the phosphorylated form of PKC-δ. The dominant-negative form of mutant PKC-δ (dnPKC-δ) reduced the IFN-α-induced JNK1 activation, TRAIL promoter activity, loss of mitochondrial membrane potential (ΔΨm), and increase in propidium iodide (PI) positive cells. The IFN-α-induced activation of JNK1 and the TRAIL promoter was also attenuated by the PKC-δ inhibitor rottlerin. Moreover, a constitutively active form of mutant PKC-δ enhanced the IFN-α-induced TRAIL promoter activity and loss of ΔΨm in Daudi B lymphoma cells. In addition, IFN-α-induced Ser727 phosphorylation of Stat1 was also abrogated by dnPKC-δ.CONCLUSIONS:
IFN-α induced JNK1 activation via PKC-δ, leading to upregulation of TRAIL. The interaction of the consequent enhanced TRAIL expression with TRAIL-receptor results in a loss of ΔΨm and increase in PI positive cells. The IFN-α-induced apoptotic events may also be affected by the Ser727-Stat1 induced by PKC-δ-mediated signaling component(s).
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Linfoma de Células B
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Interferón-alfa
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Apoptosis
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Proteínas Quinasas JNK Activadas por Mitógenos
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Proteína Quinasa C-delta
Límite:
Humans
Idioma:
En
Revista:
BMC Cell Biol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón